Genetic Variant NM_025257.3:c.17G>T (chr6-31878964-C-A) – ACMG Classification: Benign (-20 pts)

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.17G>T(p.Arg6Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0808 in 1,613,548 control chromosomes in the GnomAD database, including 7,091 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 (★★).

Frequency

Genomes: 𝑓 0.093 ( 815 hom., cov: 32)

Exomes 𝑓: 0.080 ( 6276 hom. )

Consequence

SLC44A4
NM_025257.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.853

Publications

23 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 links:

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

EHMT2-AS1 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=7.248223E-4).

BP6

Variant 6-31878964-C-A is Benign according to our data. Variant chr6-31878964-C-A is described in ClinVar as Benign. ClinVar VariationId is 1283506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.163 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.17G>T	p.Arg6Leu	missense	Exon 1 of 21	NP_079533.2	A0A140VJH4
SLC44A4	NM_001178044.2		c.17G>T	p.Arg6Leu	missense	Exon 1 of 20	NP_001171515.1	Q53GD3-4
EHMT2-AS1	NR_174947.1		n.271+886C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC44A4	ENST00000229729.11	TSL:1 MANE Select	c.17G>T	p.Arg6Leu	missense	Exon 1 of 21	ENSP00000229729.6	Q53GD3-1
SLC44A4	ENST00000414427.1	TSL:5	c.2G>T	p.Arg1Leu	missense	Exon 1 of 13	ENSP00000398901.1	H0Y5I3
SLC44A4	ENST00000882851.1		c.17G>T	p.Arg6Leu	missense	Exon 1 of 21	ENSP00000552910.1

Frequencies

GnomAD3 genomes

AF:

0.0924

AC:

14057

AN:

152062

Hom.:

816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0839

GnomAD2 exomes

AF:

0.108

AC:

27062

AN:

250636

AF XY:

0.104

show subpopulations

Gnomad AFR exome

AF:

0.0824

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.0232

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.0694

Gnomad OTH exome

AF:

0.0966

GnomAD4 exome

AF:

0.0796

AC:

116370

AN:

1461368

Hom.:

6276

Cov.:

AF XY:

0.0800

AC XY:

58171

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.0759

AC:

2542

AN:

33480

American (AMR)

AF:

0.203

AC:

9082

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0260

AC:

680

AN:

26136

East Asian (EAS)

AF:

0.182

AC:

7226

AN:

39684

South Asian (SAS)

AF:

0.121

AC:

10478

AN:

86254

European-Finnish (FIN)

AF:

0.169

AC:

8977

AN:

53158

Middle Eastern (MID)

AF:

0.0492

AC:

284

AN:

5768

European-Non Finnish (NFE)

AF:

0.0650

AC:

72216

AN:

1111818

Other (OTH)

AF:

0.0809

AC:

4885

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

5747

11494

17241

22988

28735

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2846

5692

8538

11384

14230

<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:

0.0925

AC:

14078

AN:

152180

Hom.:

815

Cov.:

AF XY:

0.0991

AC XY:

7372

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0808

AC:

3355

AN:

41524

American (AMR)

AF:

0.168

AC:

2568

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0239

AC:

AN:

3470

East Asian (EAS)

AF:

0.123

AC:

638

AN:

5166

South Asian (SAS)

AF:

0.115

AC:

552

AN:

4820

European-Finnish (FIN)

AF:

0.179

AC:

1890

AN:

10586

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0693

AC:

4716

AN:

68008

Other (OTH)

AF:

0.0835

AC:

176

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

646

1292

1938

2584

3230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

320

480

640

800

<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:

0.0737

Hom.:

1884

Bravo

AF:

0.0917

TwinsUK

AF:

0.0615

AC:

228

ALSPAC

AF:

0.0659

AC:

254

ESP6500AA

AF:

0.0783

AC:

345

ESP6500EA

AF:

0.0657

AC:

565

ExAC

AF:

0.103

AC:

12487

EpiCase

AF:

0.0632

EpiControl

AF:

0.0614

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.16

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0083

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.00072

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.85

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

REVEL

Benign

0.019

Sift

Benign

0.10

Sift4G

Benign

0.17

Polyphen

0.0020

Vest4

0.074

MPC

0.26

ClinPred

0.011

GERP RS

-3.2

PromoterAI

-0.041

Neutral

(source)

Varity_R

0.077

gMVP

0.55

Mutation Taster

=99/1

polymorphism (auto)

(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