Variant 21-42539566-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001320537.2(SLC37A1):c.405C>G(p.Leu135=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000923 in 1,613,972 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L135L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00054 ( 10 hom. )

Consequence

SLC37A1
NM_001320537.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.863

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 21-42539566-C-G is Benign according to our data. Variant chr21-42539566-C-G is described in ClinVar as [Benign]. Clinvar id is 786977.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.863 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000545 (796/1461634) while in subpopulation AFR AF= 0.017 (569/33468). AF 95% confidence interval is 0.0158. There are 10 homozygotes in gnomad4_exome. There are 344 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC37A1	NM_001320537.2 linkuse as main transcript	c.405C>G	p.Leu135=	synonymous_variant	6/20	ENST00000352133.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC37A1	ENST00000352133.3 linkuse as main transcript	c.405C>G	p.Leu135=	synonymous_variant	6/20	1	NM_001320537.2	P1
SLC37A1	ENST00000398341.7 linkuse as main transcript	c.405C>G	p.Leu135=	synonymous_variant	7/21	1		P1

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

689

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00110

AC:

277

AN:

251096

Hom.:

AF XY:

0.000811

AC XY:

110

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.000782

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000545

AC:

796

AN:

1461634

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

344

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0170

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000881

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00456

AC:

694

AN:

152338

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.0000515

Hom.:

Bravo

AF:

0.00560

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.0

DANN

Benign

0.53

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