Genetic Variant SLC16A8:p.Arg401Cys (chr22-38078702-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001394131.1(SLC16A8):c.-78C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000346 in 1,602,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

SLC16A8
NM_001394131.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

SLC16A8 (HGNC:16270): (solute carrier family 16 member 8) SLC16A8 is a member of a family of proton-coupled monocarboxylate transporters that mediate lactate transport across cell membranes (Yoon et al., 1999 [PubMed 10493836]).[supplied by OMIM, Apr 2010]

SLC16A8 links:

LOC105373027 (HGNC:):

LOC105373027 links:

Genome browser will be placed here

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
SLC16A8	NM_013356.3 link	c.1201C>T	p.Arg401Cys	missense_variant, splice_region_variant	Exon 6 of 6	ENST00000681075.2	NP_037488.2	O95907

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A8	ENST00000681075.2 link	c.1201C>T	p.Arg401Cys	missense_variant, splice_region_variant	Exon 6 of 6		NM_013356.3	ENSP00000506669.1	O95907
SLC16A8	ENST00000320521.10 link	c.1201C>T	p.Arg401Cys	missense_variant, splice_region_variant	Exon 5 of 5	1		ENSP00000321735.5	O95907
SLC16A8	ENST00000469516.5 link	n.109C>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000109

AC:

AN:

247252

Hom.:

AF XY:

0.0000894

AC XY:

AN XY:

134240

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000370

AC:

536

AN:

1449648

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

259

AN XY:

718228

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.0000755

Gnomad4 NFE exome

AF:

0.000464

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.000118

AC:

AN:

152364

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.000140

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1201C>T (p.R401C) alteration is located in exon 5 (coding exon 4) of the SLC16A8 gene. This alteration results from a C to T substitution at nucleotide position 1201, causing the arginine (R) at amino acid position 401 to be replaced by a cysteine (C). 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

0.27

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

Eigen

Benign

0.080

Eigen_PC

Benign

0.036

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.060

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.28

Sift

Benign

0.036

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.26

MVP

0.63

MPC

0.71

ClinPred

0.45

GERP RS

3.9

Varity_R

0.13

gMVP

0.48

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