chr1-112912827-C-A

Position:

• chr1-112912827-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003051.4(SLC16A1):​c.*1064G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC16A1 NM_003051.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.977

Genes affected

SLC16A1 (HGNC:10922): (solute carrier family 16 member 1) The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.*1064G>T		3_prime_UTR_variant	5/5	ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.*1064G>T		3_prime_UTR_variant	5/5		NP_001159968.1
SLC16A1	XM_047428789.1	c.*1064G>T		3_prime_UTR_variant	5/5		XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8	c.*1064G>T		3_prime_UTR_variant	5/5	1	NM_003051.4	ENSP00000358640	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 20 AN: 145574 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000658

Gnomad FIN AF: 0.000436

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000607

Gnomad OTH AF: 0.000502

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000137 AC: 20 AN: 145646 Hom.: 0 Cov.: 32 AF XY: 0.000198 AC XY: 14 AN XY: 70840

Gnomad4 AFR AF: 0.000176

Gnomad4 AMR AF: 0.0000679

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000660

Gnomad4 FIN AF: 0.000436

Gnomad4 NFE AF: 0.0000607

Gnomad4 OTH AF: 0.000497

Alfa AF: 0.00135 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Exercise-induced hyperinsulinism Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.073
DANN	Benign	0.43

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: rs886045063; hg19: chr1-113455449;