7-140348679-T-C

Position:

• chr7-140348679-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_207113.3(SLC37A3):​c.971A>G​(p.Lys324Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC37A3 NM_207113.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27002132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A3	NM_207113.3	c.971A>G	p.Lys324Arg	missense_variant	10/15	ENST00000326232.14	NP_996996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A3	ENST00000326232.14	c.971A>G	p.Lys324Arg	missense_variant	10/15	1	NM_207113.3	ENSP00000321498	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Dec 18, 2023

The c.971A>G (p.K324R) alteration is located in exon 10 (coding exon 9) of the SLC37A3 gene. This alteration results from a A to G substitution at nucleotide position 971, causing the lysine (K) at amino acid position 324 to be replaced by an arginine (R). 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	0.090
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.12	.;.;T;.
Eigen	Benign	0.17
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D;D;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.7	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	N;N;N;D
REVEL	Benign	0.15
Sift	Benign	0.18	T;T;T;.
Sift4G	Benign	0.20	T;T;T;D
Polyphen		0.0090	B;B;B;.
Vest4		0.40
MutPred		0.34		Loss of ubiquitination at K324 (P = 0.0118);Loss of ubiquitination at K324 (P = 0.0118);Loss of ubiquitination at K324 (P = 0.0118);.;
MVP		0.28
MPC		0.30
ClinPred		0.76	D
GERP RS		2.9
Varity_R		0.094
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs1796675209; hg19: chr7-140048479;