1-112912805-TA-T

Position:

• chr1-112912805-TA-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_003051.4(SLC16A1):​c.*1085del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 136,438 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (9 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: -0.312

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 -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00766 (1045/136438) while in subpopulation AFR AF= 0.0232 (865/37318). AF 95% confidence interval is 0.0219. There are 9 homozygotes in gnomad4. There are 497 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
• BS2: High Homozygotes in GnomAd4 at 9 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.*1085del		3_prime_UTR_variant	5/5	ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.*1085del		3_prime_UTR_variant	5/5		NP_001159968.1
SLC16A1	XM_047428789.1	c.*1085del		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.*1085del		3_prime_UTR_variant	5/5	1	NM_003051.4	ENSP00000358640	P1

Frequencies

GnomAD3 genomes AF: 0.00760 AC: 1037 AN: 136404 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00422

Gnomad ASJ AF: 0.00250

Gnomad EAS AF: 0.00104

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00139

Gnomad OTH AF: 0.00330

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

GnomAD4 genome AF: 0.00766 AC: 1045 AN: 136438 Hom.: 9 Cov.: 32 AF XY: 0.00753 AC XY: 497 AN XY: 65990

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.00415

Gnomad4 ASJ AF: 0.00250

Gnomad4 EAS AF: 0.00104

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00231

Gnomad4 NFE AF: 0.00139

Gnomad4 OTH AF: 0.00327

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperinsulinism, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs886045060; hg19: chr1-113455427;