rs150246870

Variant names:

• chr1-112917965-G-A
• rs150246870
• NM_003051.4:c.441C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-112917965-G-A
• chr1-112917965-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_003051.4(SLC16A1):​c.441C>T​(p.Asn147Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000604 in 1,586,788 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00063 (7 hom.)
• Consequence: SLC16A1 NM_003051.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 1.75
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 1-112917965-G-A is Benign according to our data. Variant chr1-112917965-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 258903.
• BP7: Synonymous conserved (PhyloP=1.75 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000368 (56/152128) while in subpopulation SAS AF = 0.00248 (12/4832). AF 95% confidence interval is 0.00143. There are 0 homozygotes in GnomAd4. There are 29 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AD,AR,Unknown,SD gene

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.441C>T	p.Asn147Asn	synonymous	Exon 4 of 5	NP_003042.3
	SLC16A1	NM_001166496.2		c.441C>T	p.Asn147Asn	synonymous	Exon 4 of 5	NP_001159968.1	P53985-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A1	ENST00000369626.8	TSL:1 MANE Select	c.441C>T	p.Asn147Asn	synonymous	Exon 4 of 5	ENSP00000358640.4	P53985-1
	SLC16A1	ENST00000429288.2	TSL:3	c.441C>T	p.Asn147Asn	synonymous	Exon 4 of 5	ENSP00000397106.2	P53985-1
	SLC16A1	ENST00000443580.6	TSL:3	c.441C>T	p.Asn147Asn	synonymous	Exon 4 of 5	ENSP00000399104.2	P53985-1

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152128 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000389 AC: 86 AN: 221116 AF XY: 0.000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000764

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000381

Gnomad OTH exome AF: 0.000386

GnomAD4 exome AF: 0.000629 AC: 902 AN: 1434660 Hom.: 7 Cov.: 32 AF XY: 0.000655 AC XY: 467 AN XY: 713186

African (AFR) AF: 0.0000634 AC: 2 AN: 31566

American (AMR) AF: 0.000138 AC: 5 AN: 36162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24406

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00181 AC: 146 AN: 80578

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5592

European-Non Finnish (NFE) AF: 0.000661 AC: 730 AN: 1105032

Other (OTH) AF: 0.000305 AC: 18 AN: 59098

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152128 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74316

African (AFR) AF: 0.000145 AC: 6 AN: 41412

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00248 AC: 12 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.000397 Hom.: 0

Bravo AF: 0.000317

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	Exercise-induced hyperinsulinism (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.48
PhyloP100		1.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs150246870; hg19: chr1-113460587;