rs1049434

Variant names:

• chr1-112913924-A-T
• rs1049434
• NM_003051.4:c.1470T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-112913924-A-T
• chr1-112913924-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003051.4(SLC16A1):​c.1470T>A​(p.Asp490Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,613,802 control chromosomes in the GnomAD database, including 278,152 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (33924 hom., cov: 32)
  • Exomes 𝑓: 0.57 (244228 hom.)
• Consequence: SLC16A1 NM_003051.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.105
• Publications: 148 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.3899806E-7).
• BP6: Variant 1-112913924-A-T is Benign according to our data. Variant chr1-112913924-A-T is described in ClinVar as Benign. ClinVar VariationId is 130315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

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.1470T>A	p.Asp490Glu	missense	Exon 5 of 5	NP_003042.3
	SLC16A1	NM_001166496.2		c.1470T>A	p.Asp490Glu	missense	Exon 5 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.1470T>A	p.Asp490Glu	missense	Exon 5 of 5	ENSP00000358640.4	P53985-1
	SLC16A1	ENST00000429288.2	TSL:3	c.1470T>A	p.Asp490Glu	missense	Exon 5 of 5	ENSP00000397106.2	P53985-1
	SLC16A1	ENST00000443580.6	TSL:3	c.1470T>A	p.Asp490Glu	missense	Exon 5 of 5	ENSP00000399104.2	P53985-1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99407 AN: 151898 Hom.: 33864 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.645

GnomAD2 exomes AF: 0.592 AC: 148782 AN: 251466 AF XY: 0.587

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.522

Gnomad ASJ exome AF: 0.631

Gnomad EAS exome AF: 0.670

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.592

GnomAD4 exome AF: 0.575 AC: 840521 AN: 1461786 Hom.: 244228 Cov.: 59 AF XY: 0.574 AC XY: 417382 AN XY: 727198

African (AFR) AF: 0.866 AC: 29006 AN: 33478

American (AMR) AF: 0.529 AC: 23658 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 16439 AN: 26134

East Asian (EAS) AF: 0.665 AC: 26399 AN: 39696

South Asian (SAS) AF: 0.547 AC: 47197 AN: 86256

European-Finnish (FIN) AF: 0.577 AC: 30795 AN: 53416

Middle Eastern (MID) AF: 0.644 AC: 3713 AN: 5766

European-Non Finnish (NFE) AF: 0.564 AC: 627570 AN: 1111922

Other (OTH) AF: 0.592 AC: 35744 AN: 60394

GnomAD4 genome AF: 0.655 AC: 99530 AN: 152016 Hom.: 33924 Cov.: 32 AF XY: 0.652 AC XY: 48465 AN XY: 74298

African (AFR) AF: 0.856 AC: 35546 AN: 41502

American (AMR) AF: 0.565 AC: 8630 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.635 AC: 2202 AN: 3466

East Asian (EAS) AF: 0.661 AC: 3407 AN: 5158

South Asian (SAS) AF: 0.567 AC: 2727 AN: 4812

European-Finnish (FIN) AF: 0.586 AC: 6181 AN: 10546

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38749 AN: 67940

Other (OTH) AF: 0.649 AC: 1374 AN: 2116

Alfa AF: 0.589 Hom.: 20138

Bravo AF: 0.662

TwinsUK AF: 0.565 AC: 2096

ALSPAC AF: 0.568 AC: 2189

ESP6500AA AF: 0.845 AC: 3721

ESP6500EA AF: 0.575 AC: 4944

ExAC AF: 0.597 AC: 72494

Asia WGS AF: 0.635 AC: 2209 AN: 3478

EpiCase AF: 0.575

EpiControl AF: 0.581

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Exercise-induced hyperinsulinism (2)
-	-	1	Ketoacidosis due to monocarboxylate transporter-1 deficiency (1)
-	-	1	Metabolic myopathy due to lactate transporter defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.15
DEOGEN2	Benign	0.071	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0076	N
MetaRNN	Benign	8.4e-7	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.10
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.14		Gain of glycosylation at P493 (P = 0.16)
MPC		0.31
ClinPred		0.0057	T
GERP RS		2.7
Varity_R		0.051
gMVP		0.094
Mutation Taster		=98/2	polymorphism (auto)

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: rs1049434; hg19: chr1-113456546; COSMIC: COSV63710018; COSMIC: COSV63710018;