Genetic Variant SLC16A11:p.Ala431Thr (chr17-7041732-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001370549.1(SLC16A11):c.1291G>A(p.Ala431Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,012 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SLC16A11
NM_001370549.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.334

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043694794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A11	NM_001370549.1 link	c.1291G>A	p.Ala431Thr	missense_variant	Exon 5 of 5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3 link	c.1291G>A	p.Ala431Thr	missense_variant	Exon 4 of 4		NP_699188.2	Q8NCK7
SLC16A11	NM_001370553.1 link	c.*199G>A		3_prime_UTR_variant	Exon 4 of 4		NP_001357482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A11	ENST00000574600.3 link	c.1291G>A	p.Ala431Thr	missense_variant	Exon 5 of 5	3	NM_001370549.1	ENSP00000460927.2	I3L431
SLC16A11	ENST00000573338.1 link	n.854G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1
SLC16A11	ENST00000662352.3 link	c.1291G>A	p.Ala431Thr	missense_variant	Exon 4 of 4			ENSP00000499634.1	I3L431
SLC16A11	ENST00000673828 link	c.*199G>A		3_prime_UTR_variant	Exon 4 of 4			ENSP00000501313.1	A0A669KBK5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248190

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134846

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1460998

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726758

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1363G>A (p.A455T) alteration is located in exon 4 (coding exon 4) of the SLC16A11 gene. This alteration results from a G to A substitution at nucleotide position 1363, causing the alanine (A) at amino acid position 455 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.49

DANN

Benign

0.84

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.20

N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.010

N;N

REVEL

Benign

0.0070

Sift

Benign

0.75

T;T

Sift4G

Benign

0.072

T;T

Polyphen

0.020

B;.

Vest4

0.20

MutPred

0.25

Gain of glycosylation at A455 (P = 0.032);.;

MVP

0.040

MPC

0.32

ClinPred

0.018

GERP RS

0.74

Varity_R

0.028

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over