rs150385253

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_025257.3(SLC44A4):c.2059A>G(p.Met687Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,612,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

SLC44A4
NM_025257.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 7.54

Publications

3 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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08819413).

BP6

Variant 6-31863701-T-C is Benign according to our data. Variant chr6-31863701-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2212653.

BS2

High AC in GnomAd4 at 66 AD gene.

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.2059A>G	p.Met687Val	missense	Exon 21 of 21	NP_079533.2	A0A140VJH4
SLC44A4	NM_001178044.2		c.1933A>G	p.Met645Val	missense	Exon 20 of 20	NP_001171515.1	Q53GD3-4
SLC44A4	NM_001178045.2		c.1831A>G	p.Met611Val	missense	Exon 21 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.2059A>G	p.Met687Val	missense	Exon 21 of 21	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000882851.1		c.2125A>G	p.Met709Val	missense	Exon 21 of 21	ENSP00000552910.1
SLC44A4	ENST00000882853.1		c.2092A>G	p.Met698Val	missense	Exon 21 of 21	ENSP00000552912.1

Frequencies

GnomAD3 genomes

AF:

0.000441

AC:

AN:

151952

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000172

AC:

AN:

244810

AF XY:

0.000142

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.000467

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000746

AC:

109

AN:

1460330

Hom.:

Cov.:

AF XY:

0.0000716

AC XY:

AN XY:

726484

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

33454

American (AMR)

AF:

0.000492

AC:

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39662

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.0000382

AC:

AN:

52306

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111736

Other (OTH)

AF:

0.0000994

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000434

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

41462

American (AMR)

AF:

0.000458

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000155

Hom.:

Bravo

AF:

0.000495

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00232

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000187

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.030

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

PhyloP100

7.5

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.41

Sift

Benign

0.14

Sift4G

Uncertain

0.039

Polyphen

0.95

Vest4

0.74

MVP

0.22

MPC

0.67

ClinPred

0.084

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.70

gMVP

0.94

Mutation Taster

=22/78

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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