Variant chr21-42534767-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001320537.2(SLC37A1):c.208T>A(p.Ser70Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Consequence

SLC37A1
NM_001320537.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.271

Variant links:

Genes affected

SLC37A1 (HGNC:11024): (solute carrier family 37 member 1) The protein encoded by this gene localizes to the endoplasmic reticulum (ER) membrane. This protein translocates glucose-6-phosphate from the cytoplasm into the lumen of the ER for hydrolysis into glucose by another ER membrane protein. This gene is a member of the solute carrier 37 gene family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SLC37A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.046541363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A1	NM_001320537.2 linkuse as main transcript	c.208T>A	p.Ser70Thr	missense_variant	4/20	ENST00000352133.3	NP_001307466.1	P57057

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A1	ENST00000352133.3 linkuse as main transcript	c.208T>A	p.Ser70Thr	missense_variant	4/20	1	NM_001320537.2	ENSP00000344648.2		P57057
SLC37A1	ENST00000398341.7 linkuse as main transcript	c.208T>A	p.Ser70Thr	missense_variant	5/21	1		ENSP00000381383.3		P57057

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152088

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.208T>A (p.S70T) alteration is located in exon 5 (coding exon 3) of the SLC37A1 gene. This alteration results from a T to A substitution at nucleotide position 208, causing the serine (S) at amino acid position 70 to be replaced by a threonine (T). 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

0.061

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.55

DANN

Benign

0.55

DEOGEN2

Benign

0.029

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.99

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.0080

Sift

Benign

0.58

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.40

Loss of glycosylation at S70 (P = 0.0618);Loss of glycosylation at S70 (P = 0.0618);

MVP

0.088

MPC

0.35

ClinPred

0.043

GERP RS

-0.38

Varity_R

0.051

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over