Genetic Variant SLC16A11:p.Gly395Arg (chr17-7041840-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370549.1(SLC16A11):c.1183G>C(p.Gly395Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SLC16A11
NM_001370549.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.72

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A11	NM_001370549.1 link	c.1183G>C	p.Gly395Arg	missense_variant	Exon 5 of 5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3 link	c.1183G>C	p.Gly395Arg	missense_variant	Exon 4 of 4		NP_699188.2	Q8NCK7
SLC16A11	NM_001370553.1 link	c.*91G>C		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.1183G>C	p.Gly395Arg	missense_variant	Exon 5 of 5	3	NM_001370549.1	ENSP00000460927.2	I3L431
SLC16A11	ENST00000573338.1 link	n.746G>C		non_coding_transcript_exon_variant	Exon 2 of 2	1
SLC16A11	ENST00000662352.3 link	c.1183G>C	p.Gly395Arg	missense_variant	Exon 4 of 4			ENSP00000499634.1	I3L431
SLC16A11	ENST00000673828 link	c.*91G>C		3_prime_UTR_variant	Exon 4 of 4			ENSP00000501313.1	A0A669KBK5

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000532

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000722

AC:

AN:

249456

Hom.:

AF XY:

0.0000590

AC XY:

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.000840

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000158

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.000532

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000992

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1255G>C (p.G419R) alteration is located in exon 4 (coding exon 4) of the SLC16A11 gene. This alteration results from a G to C substitution at nucleotide position 1255, causing the glycine (G) at amino acid position 419 to be replaced by an arginine (R). 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.86

D;D

M_CAP

Benign

0.059

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.80

MVP

0.81

MPC

1.2

ClinPred

0.90

GERP RS

5.1

Varity_R

0.72

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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