rs606231312

Variant names:

• chr1-112917915-A-AG
• rs606231312
• NM_003051.4:c.490dupC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_003051.4(SLC16A1):​c.490dupC​(p.Leu164ProfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,453,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SLC16A1 NM_003051.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: -0.121
• Publications: 3 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 1-112917915-A-AG is Pathogenic according to our data. Variant chr1-112917915-A-AG is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 160372.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003051.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1	NM_003051.4	MANE Select	c.490dupC	p.Leu164ProfsTer46	frameshift	Exon 4 of 5	NP_003042.3
	SLC16A1	NM_001166496.2		c.490dupC	p.Leu164ProfsTer46	frameshift	Exon 4 of 5	NP_001159968.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1	ENST00000369626.8	TSL:1 MANE Select	c.490dupC	p.Leu164ProfsTer46	frameshift	Exon 4 of 5	ENSP00000358640.4
	SLC16A1	ENST00000429288.2	TSL:3	c.490dupC	p.Leu164ProfsTer46	frameshift	Exon 4 of 5	ENSP00000397106.2
	SLC16A1	ENST00000443580.6	TSL:3	c.490dupC	p.Leu164ProfsTer46	frameshift	Exon 4 of 5	ENSP00000399104.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000482 AC: 7 AN: 1453714 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722764

African (AFR) AF: 0.00 AC: 0 AN: 32880

American (AMR) AF: 0.00 AC: 0 AN: 43124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25554

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000631 AC: 7 AN: 1108630

Other (OTH) AF: 0.00 AC: 0 AN: 59950

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Monocarboxylate transporter 1 deficiency, autosomal dominant (1)
1	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.12
Mutation Taster		=5/195	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs606231312; hg19: chr1-113460537; COSMIC: COSV63710370; COSMIC: COSV63710370;