1-112918054-C-CAATA

Position:

• chr1-112918054-C-CAATA

Variant summary

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

The NM_003051.4(SLC16A1):​c.362-11_362-10insTATT variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -0.497

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 Benign. Variant got -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 id is 1336772.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
• 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A1	NM_003051.4	c.362-11_362-10insTATT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000369626.8	NP_003042.3
SLC16A1	NM_001166496.2	c.362-11_362-10insTATT		splice_polypyrimidine_tract_variant, intron_variant			NP_001159968.1
SLC16A1	XM_047428789.1	c.362-11_362-10insTATT		splice_polypyrimidine_tract_variant, intron_variant			XP_047284745.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A1	ENST00000369626.8	c.362-11_362-10insTATT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003051.4	ENSP00000358640	P1

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

GnomAD3 exomes AF: 0.000856 AC: 52 AN: 60732 Hom.: 0 AF XY: 0.000813 AC XY: 29 AN XY: 35678

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 SAS exome AF: 0.000970

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

Gnomad4 AFR exome AF: 0.00779

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.000909

Gnomad4 EAS exome AF: 0.00144

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.00531

Gnomad4 NFE exome AF: 0.00247

Gnomad4 OTH exome AF: 0.00273

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

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.000582

Gnomad4 EAS AF: 0.00421

Gnomad4 SAS AF: 0.00133

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.00393

Gnomad4 OTH AF: 0.00700

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2022	SLC16A1: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Nov 11, 2019

- -

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;