1-112918054-CAATAAATAAATAAATAAATAAATAAATAAATA-CAATAAATAAATAAATAAATAAATAAATAAATAAATA

Variant names:

• chr1-112918054-C-CAATA
• rs149491709
• NM_003051.4:c.362-14_362-11dupTATT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_003051.4(SLC16A1):​c.362-14_362-11dupTATT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0064 (5 hom., cov: 0)
  • Exomes 𝑓: 0.0026 (2 hom.)
• Consequence: SLC16A1 NM_003051.4 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.497
• Publications: 1 publications found

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-AS1 (HGNC:49445): (SLC16A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 1-112918054-C-CAATA is Benign according to our data. Variant chr1-112918054-C-CAATA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1336772.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00643 (930/144614) while in subpopulation AFR AF = 0.0102 (395/38742). AF 95% confidence interval is 0.00937. There are 5 homozygotes in GnomAd4. There are 476 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR,Unknown,SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.362-14_362-11dupTATT		intron_variant	Intron 3 of 4	ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.362-14_362-11dupTATT		intron_variant	Intron 3 of 4		NP_001159968.1
SLC16A1	XM_047428789.1	c.362-14_362-11dupTATT		intron_variant	Intron 3 of 4		XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8	c.362-11_362-10insTATT		intron_variant	Intron 3 of 4	1	NM_003051.4	ENSP00000358640.4

Frequencies

GnomAD3 genomes AF: 0.00644 AC: 931 AN: 144542 Hom.: 5 Cov.: 0

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.000582

Gnomad EAS AF: 0.00440

Gnomad SAS AF: 0.00132

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.00708

GnomAD2 exomes AF: 0.000856 AC: 52 AN: 60732 AF XY: 0.000813

Gnomad AFR exome AF: 0.000302

Gnomad AMR exome AF: 0.000227

Gnomad ASJ exome AF: 0.000308

Gnomad EAS exome AF: 0.00114

Gnomad FIN exome AF: 0.00231

Gnomad NFE exome AF: 0.000770

Gnomad OTH exome AF: 0.000795

GnomAD4 exome AF: 0.00256 AC: 1830 AN: 714864 Hom.: 2 Cov.: 0 AF XY: 0.00250 AC XY: 904 AN XY: 361898

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00779 AC: 114 AN: 14632

American (AMR) AF: 0.00201 AC: 26 AN: 12938

Ashkenazi Jewish (ASJ) AF: 0.000909 AC: 13 AN: 14298

East Asian (EAS) AF: 0.00144 AC: 35 AN: 24286

South Asian (SAS) AF: 0.00148 AC: 34 AN: 22962

European-Finnish (FIN) AF: 0.00531 AC: 111 AN: 20920

Middle Eastern (MID) AF: 0.000903 AC: 2 AN: 2214

European-Non Finnish (NFE) AF: 0.00247 AC: 1411 AN: 571870

Other (OTH) AF: 0.00273 AC: 84 AN: 30744

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00643 AC: 930 AN: 144614 Hom.: 5 Cov.: 0 AF XY: 0.00678 AC XY: 476 AN XY: 70210

African (AFR) AF: 0.0102 AC: 395 AN: 38742

American (AMR) AF: 0.00523 AC: 76 AN: 14534

Ashkenazi Jewish (ASJ) AF: 0.000582 AC: 2 AN: 3438

East Asian (EAS) AF: 0.00421 AC: 21 AN: 4984

South Asian (SAS) AF: 0.00133 AC: 6 AN: 4518

European-Finnish (FIN) AF: 0.0174 AC: 153 AN: 8794

Middle Eastern (MID) AF: 0.00704 AC: 2 AN: 284

European-Non Finnish (NFE) AF: 0.00393 AC: 261 AN: 66416

Other (OTH) AF: 0.00700 AC: 14 AN: 2000

Alfa AF: 0.00500 Hom.: 967

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC16A1: BS2 -

not specified Uncertain:1

Nov 11, 2019

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs149491709; hg19: chr1-113460676;