rs1399925

Positions:

• chr21-42571832-A-G
• chr21-42571832-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000352133.3(SLC37A1):​c.1424-2986A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 151,994 control chromosomes in the GnomAD database, including 42,580 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42580 hom., cov: 31)
• Consequence: SLC37A1 ENST00000352133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A1	NM_001320537.2	c.1424-2986A>G		intron_variant		ENST00000352133.3	NP_001307466.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A1	ENST00000352133.3	c.1424-2986A>G		intron_variant		1	NM_001320537.2	ENSP00000344648	P1
SLC37A1	ENST00000398341.7	c.1424-2986A>G		intron_variant		1		ENSP00000381383	P1
SLC37A1	ENST00000496416.1	n.203-2986A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112411 AN: 151876 Hom.: 42546 Cov.: 31

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.729

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112508 AN: 151994 Hom.: 42580 Cov.: 31 AF XY: 0.733 AC XY: 54488 AN XY: 74296

Gnomad4 AFR AF: 0.811

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.725

Alfa AF: 0.729 Hom.: 4769

Bravo AF: 0.749

Asia WGS AF: 0.452 AC: 1572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.28

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: rs1399925; hg19: chr21-43991942;