21-42539566-C-T

Variant names:

• chr21-42539566-C-T
• rs116869533
• NM_001320537.2:c.405C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001320537.2(SLC37A1):​c.405C>T​(p.Leu135Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,944 control chromosomes in the GnomAD database, including 150 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 0.0097 (22 hom., cov: 33)
  • Exomes 𝑓: 0.012 (128 hom.)
• Consequence: SLC37A1 NM_001320537.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.863
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 21-42539566-C-T is Benign according to our data. Variant chr21-42539566-C-T is described in ClinVar as [Benign]. Clinvar id is 777310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.863 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC37A1	NM_001320537.2	c.405C>T	p.Leu135Leu	synonymous_variant	Exon 6 of 20	ENST00000352133.3	NP_001307466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC37A1	ENST00000352133.3	c.405C>T	p.Leu135Leu	synonymous_variant	Exon 6 of 20	1	NM_001320537.2	ENSP00000344648.2
SLC37A1	ENST00000398341.7	c.405C>T	p.Leu135Leu	synonymous_variant	Exon 7 of 21	1		ENSP00000381383.3

Frequencies

GnomAD3 genomes AF: 0.00970 AC: 1477 AN: 152222 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00236

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.0227

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00959 AC: 2408 AN: 251096 AF XY: 0.00998

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00261

Gnomad ASJ exome AF: 0.00586

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0217

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.00767

GnomAD4 exome AF: 0.0117 AC: 17128 AN: 1461604 Hom.: 128 Cov.: 30 AF XY: 0.0117 AC XY: 8498 AN XY: 727090

African (AFR) AF: 0.00131 AC: 44 AN: 33468

American (AMR) AF: 0.00338 AC: 151 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00586 AC: 153 AN: 26126

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39658

South Asian (SAS) AF: 0.00709 AC: 611 AN: 86216

European-Finnish (FIN) AF: 0.0212 AC: 1133 AN: 53404

Middle Eastern (MID) AF: 0.00745 AC: 43 AN: 5768

European-Non Finnish (NFE) AF: 0.0130 AC: 14418 AN: 1111908

Other (OTH) AF: 0.00949 AC: 573 AN: 60382

GnomAD4 genome AF: 0.00969 AC: 1476 AN: 152340 Hom.: 22 Cov.: 33 AF XY: 0.00961 AC XY: 716 AN XY: 74496

African (AFR) AF: 0.00236 AC: 98 AN: 41572

American (AMR) AF: 0.00451 AC: 69 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00498 AC: 24 AN: 4818

European-Finnish (FIN) AF: 0.0227 AC: 241 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 893 AN: 68042

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00745 Hom.: 3

Bravo AF: 0.00884

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.2
DANN	Benign	0.64
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116869533; hg19: chr21-43959676;