Genetic Variant NM_001370549.1:c.761G>A (chr17-7042349-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370549.1(SLC16A11):c.761G>A(p.Gly254Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,406,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G254R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC16A11
NM_001370549.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.328

Publications

0 publications found

Variant links:

Genes affected

SLC16A11 (HGNC:23093): (solute carrier family 16 member 11) Enables pyruvate transmembrane transporter activity. Involved in lipid metabolic process. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC16A11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08324942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370549.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A11	NM_001370549.1	MANE Select	c.761G>A	p.Gly254Glu	missense	Exon 4 of 5	NP_001357478.1	I3L431
SLC16A11	NM_153357.3		c.761G>A	p.Gly254Glu	missense	Exon 3 of 4	NP_699188.2	I3L431
SLC16A11	NM_001370553.1		c.761G>A	p.Gly254Glu	missense	Exon 4 of 4	NP_001357482.1	A0A669KBK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC16A11	ENST00000574600.3	TSL:3 MANE Select	c.761G>A	p.Gly254Glu	missense	Exon 4 of 5	ENSP00000460927.2	I3L431
SLC16A11	ENST00000573338.1	TSL:1	n.678-441G>A		intron	N/A
SLC16A11	ENST00000662352.3		c.761G>A	p.Gly254Glu	missense	Exon 3 of 4	ENSP00000499634.1	I3L431

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000601

AC:

AN:

166484

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1406422

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694270

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31970

American (AMR)

AF:

0.00

AC:

AN:

38022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25032

East Asian (EAS)

AF:

0.00

AC:

AN:

36448

South Asian (SAS)

AF:

0.0000250

AC:

AN:

79976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48834

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082340

Other (OTH)

AF:

0.00

AC:

AN:

58124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.032

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.76

M_CAP

Benign

0.011

MetaRNN

Benign

0.083

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.66

PhyloP100

0.33

PrimateAI

Uncertain

0.55

PROVEAN

Benign

1.3

REVEL

Benign

0.21

Sift

Benign

0.63

Sift4G

Benign

0.35

Polyphen

0.38

Vest4

0.20

MutPred

0.60

Gain of stability (P = 0.0553)

MVP

0.37

MPC

1.2

ClinPred

0.23

GERP RS

5.0

Varity_R

0.15

gMVP

0.51

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over