Genetic Variant SLC37A3:p.Gly373Arg (chr7-140345878-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_207113.3(SLC37A3):c.1117G>C(p.Gly373Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,646 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC37A3
NM_207113.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

Publications

0 publications found

Variant links:

Genes affected

SLC37A3 (HGNC:20651): (solute carrier family 37 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in carbohydrate transport and transmembrane transport. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC37A3 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics

SLC37A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207113.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC37A3	NM_207113.3	MANE Select	c.1117G>C	p.Gly373Arg	missense	Exon 11 of 15	NP_996996.1	Q8NCC5-1
SLC37A3	NM_001363373.1		c.1117G>C	p.Gly373Arg	missense	Exon 11 of 14	NP_001350302.1
SLC37A3	NM_001287498.2		c.1117G>C	p.Gly373Arg	missense	Exon 11 of 14	NP_001274427.1	Q8NCC5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC37A3	ENST00000326232.14	TSL:1 MANE Select	c.1117G>C	p.Gly373Arg	missense	Exon 11 of 15	ENSP00000321498.9	Q8NCC5-1
SLC37A3	ENST00000447932.6	TSL:1	c.1117G>C	p.Gly373Arg	missense	Exon 11 of 14	ENSP00000397481.2	Q8NCC5-2
SLC37A3	ENST00000340308.7	TSL:1	c.1024+2748G>C		intron	N/A	ENSP00000343358.3	Q8NCC5-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250544

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460646

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726714

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110962

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.3

PhyloP100

7.1

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.39

Sift

Benign

0.16

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.89

MutPred

0.53

Loss of catalytic residue at S375 (P = 0.0447)

MVP

0.64

MPC

0.96

ClinPred

0.89

GERP RS

5.0

PromoterAI

0.045

Neutral

(source)

Varity_R

0.21

gMVP

0.88

Mutation Taster

=5/95

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over