7-140358785-C-A

Position:

• chr7-140358785-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207113.3(SLC37A3):​c.376G>T​(p.Val126Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC37A3 NM_207113.3 missense, splice_region
• Scores: Splicing: ADA: 0.9942
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A3	NM_207113.3	c.376G>T	p.Val126Leu	missense_variant, splice_region_variant	6/15	ENST00000326232.14	NP_996996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A3	ENST00000326232.14	c.376G>T	p.Val126Leu	missense_variant, splice_region_variant	6/15	1	NM_207113.3	ENSP00000321498	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.376G>T (p.V126L) alteration is located in exon 6 (coding exon 5) of the SLC37A3 gene. This alteration results from a G to T substitution at nucleotide position 376, causing the valine (V) at amino acid position 126 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	.;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.0	L;L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.10
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.019	B;B;B
Vest4		0.56
MutPred		0.68		Loss of catalytic residue at V126 (P = 0.0479);Loss of catalytic residue at V126 (P = 0.0479);Loss of catalytic residue at V126 (P = 0.0479);
MVP		0.43
MPC		0.28
ClinPred		0.69	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.97
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: -25

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

Publications

LitVar

Other links and lift over

dbSNP: rs1486514231; hg19: chr7-140058585;