chr1-112912819-C-A

Position:

• chr1-112912819-C-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BS1_Supporting

The NM_003051.4(SLC16A1):​c.*1072G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000525 in 142,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (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: -2.61

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000525 (75/142844) while in subpopulation AFR AF= 0.000825 (32/38810). AF 95% confidence interval is 0.0006. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.*1072G>T		3_prime_UTR_variant	5/5	ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.*1072G>T		3_prime_UTR_variant	5/5		NP_001159968.1
SLC16A1	XM_047428789.1	c.*1072G>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.*1072G>T		3_prime_UTR_variant	5/5	1	NM_003051.4	ENSP00000358640	P1

Frequencies

GnomAD3 genomes AF: 0.000518 AC: 74 AN: 142780 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000801

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000278

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000409

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.00149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00102

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.000525 AC: 75 AN: 142844 Hom.: 0 Cov.: 32 AF XY: 0.000649 AC XY: 45 AN XY: 69364

Gnomad4 AFR AF: 0.000825

Gnomad4 AMR AF: 0.000278

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000411

Gnomad4 SAS AF: 0.000221

Gnomad4 FIN AF: 0.00149

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00101

Alfa AF: 0.00288 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 13, 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	-0.94
CADD	Benign	0.062
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: rs886045062; hg19: chr1-113455441;