1-112918054-CAATAAATAAATAAATAAATAAATA-CAATAAATAAATA

Position:

• chr1-112918054-CAATAAATAAATAAATAAATAAATA-CAATAAATAAATA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_003051.4(SLC16A1):​c.362-22_362-11delTATTTATTTATT variant causes a intron change. The variant allele was found at a frequency of 0.0181 in 857,606 control chromosomes in the GnomAD database, including 240 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.016 (23 hom., cov: 0)
  • Exomes 𝑓: 0.018 (217 hom.)
• Consequence: SLC16A1 NM_003051.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 3.97

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]

SLC16A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 1-112918054-CAATAAATAAATA-C is Benign according to our data. Variant chr1-112918054-CAATAAATAAATA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 212184.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=2}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0161 (2322/144598) while in subpopulation NFE AF= 0.0173 (1148/66406). AF 95% confidence interval is 0.0165. There are 23 homozygotes in gnomad4. There are 1171 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.362-22_362-11delTATTTATTTATT		intron_variant		ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.362-22_362-11delTATTTATTTATT		intron_variant			NP_001159968.1
SLC16A1	XM_047428789.1	c.362-22_362-11delTATTTATTTATT		intron_variant			XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8	c.362-22_362-11delTATTTATTTATT		intron_variant		1	NM_003051.4	ENSP00000358640.4

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 2319 AN: 144526 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00996

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.0244

Gnomad EAS AF: 0.00901

Gnomad SAS AF: 0.00595

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0162

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0258

GnomAD3 exomes AF: 0.00795 AC: 483 AN: 60732 Hom.: 19 AF XY: 0.00807 AC XY: 288 AN XY: 35678

Gnomad AFR exome AF: 0.00121

Gnomad AMR exome AF: 0.00453

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.00420

Gnomad SAS exome AF: 0.00558

Gnomad FIN exome AF: 0.0129

Gnomad NFE exome AF: 0.00783

Gnomad OTH exome AF: 0.00954

GnomAD4 exome AF: 0.0185 AC: 13180 AN: 713008 Hom.: 217 AF XY: 0.0181 AC XY: 6543 AN XY: 360876

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0210

Gnomad4 EAS exome AF: 0.00276

Gnomad4 SAS exome AF: 0.00690

Gnomad4 FIN exome AF: 0.0211

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0161 AC: 2322 AN: 144598 Hom.: 23 Cov.: 0 AF XY: 0.0167 AC XY: 1171 AN XY: 70192

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.0244

Gnomad4 EAS AF: 0.00883

Gnomad4 SAS AF: 0.00598

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0265

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 03, 2023	- -

Hyperinsulinism, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 22, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149491709; hg19: chr1-113460676;