rs2242665

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025257.3(SLC44A4):c.559G>A(p.Val187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,611,384 control chromosomes in the GnomAD database, including 260,629 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V187T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.60 ( 27739 hom., cov: 30)

Exomes 𝑓: 0.56 ( 232890 hom. )

Consequence

SLC44A4
NM_025257.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.113

Publications

76 publications found

Variant links:

Genes affected

SLC44A4 (HGNC:13941): (solute carrier family 44 member 4) The protein encoded by this gene may be a sodium-dependent transmembrane transport protein involved in the uptake of choline by cholinergic neurons. Defects in this gene can cause sialidosis, a lysosomal storage disease. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC44A4 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal dominant 72
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

SLC44A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.7938253E-6).

BP6

Variant 6-31871532-C-T is Benign according to our data. Variant chr6-31871532-C-T is described in ClinVar as Benign. ClinVar VariationId is 1224894.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025257.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A4	NM_025257.3	MANE Select	c.559G>A	p.Val187Ile	missense	Exon 8 of 21	NP_079533.2	A0A140VJH4
SLC44A4	NM_001178044.2		c.433G>A	p.Val145Ile	missense	Exon 7 of 20	NP_001171515.1	Q53GD3-4
SLC44A4	NM_001178045.2		c.331G>A	p.Val111Ile	missense	Exon 8 of 21	NP_001171516.1	A0A1U9X8K7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.559G>A	p.Val187Ile	missense	Exon 8 of 21	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000414427.1	TSL:5	c.544G>A	p.Val182Ile	missense	Exon 8 of 13	ENSP00000398901.1	H0Y5I3
SLC44A4	ENST00000882851.1		c.559G>A	p.Val187Ile	missense	Exon 8 of 21	ENSP00000552910.1

Frequencies

GnomAD3 genomes

AF:

0.599

AC:

90739

AN:

151590

Hom.:

27710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.579

Gnomad AMR

AF:

0.643

Gnomad ASJ

AF:

0.811

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.604

Gnomad FIN

AF:

0.429

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.660

GnomAD2 exomes

AF:

0.597

AC:

149871

AN:

250964

AF XY:

0.599

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.646

Gnomad ASJ exome

AF:

0.816

Gnomad EAS exome

AF:

0.609

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.574

Gnomad OTH exome

AF:

0.614

GnomAD4 exome

AF:

0.560

AC:

816789

AN:

1459676

Hom.:

232890

Cov.:

AF XY:

0.564

AC XY:

409711

AN XY:

726240

show subpopulations

African (AFR)

AF:

0.676

AC:

22616

AN:

33442

American (AMR)

AF:

0.649

AC:

29004

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.810

AC:

21163

AN:

26134

East Asian (EAS)

AF:

0.630

AC:

24982

AN:

39674

South Asian (SAS)

AF:

0.621

AC:

53513

AN:

86214

European-Finnish (FIN)

AF:

0.432

AC:

23077

AN:

53392

Middle Eastern (MID)

AF:

0.790

AC:

4549

AN:

5760

European-Non Finnish (NFE)

AF:

0.543

AC:

602887

AN:

1110046

Other (OTH)

AF:

0.580

AC:

34998

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

20311

40622

60932

81243

101554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16980

33960

50940

67920

84900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.599

AC:

90828

AN:

151708

Hom.:

27739

Cov.:

AF XY:

0.595

AC XY:

44092

AN XY:

74116

show subpopulations

African (AFR)

AF:

0.671

AC:

27749

AN:

41332

American (AMR)

AF:

0.642

AC:

9793

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.811

AC:

2812

AN:

3466

East Asian (EAS)

AF:

0.598

AC:

3078

AN:

5150

South Asian (SAS)

AF:

0.605

AC:

2907

AN:

4804

European-Finnish (FIN)

AF:

0.429

AC:

4514

AN:

10530

Middle Eastern (MID)

AF:

0.779

AC:

229

AN:

294

European-Non Finnish (NFE)

AF:

0.557

AC:

37824

AN:

67862

Other (OTH)

AF:

0.662

AC:

1395

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1742

3484

5227

6969

8711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

760

1520

2280

3040

3800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.582

Hom.:

100268

Bravo

AF:

0.621

TwinsUK

AF:

0.544

AC:

2016

ALSPAC

AF:

0.545

AC:

2100

ESP6500AA

AF:

0.661

AC:

2911

ESP6500EA

AF:

0.558

AC:

4800

ExAC

AF:

0.598

AC:

72561

Asia WGS

AF:

0.601

AC:

2095

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hearing loss, autosomal dominant 72 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.16

(source)

DANN

Benign

0.59

DEOGEN2

Benign

0.0037

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0020

MetaRNN

Benign

0.0000018

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

PhyloP100

-0.11

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.23

REVEL

Benign

0.0090

Sift

Benign

0.45

Sift4G

Benign

0.74

Polyphen

0.0

Vest4

0.020

MPC

0.17

ClinPred

0.0069

GERP RS

0.52

Varity_R

0.015

gMVP

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over