Genetic Variant SLC16A8:p.Arg339His (chr22-38081022-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_013356.3(SLC16A8):c.1016G>A(p.Arg339His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,310 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC16A8
NM_013356.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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:

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.1016G>A	p.Arg339His	missense_variant	Exon 5 of 6	ENST00000681075.2	NP_037488.2	O95907
SLC16A8	XM_017028685.2 link	c.1016G>A	p.Arg339His	missense_variant	Exon 3 of 4		XP_016884174.1	O95907
SLC16A8	NM_001394131.1 link	c.-80-2318G>A		intron_variant	Intron 1 of 1		NP_001381060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC16A8	ENST00000681075.2 link	c.1016G>A	p.Arg339His	missense_variant	Exon 5 of 6		NM_013356.3	ENSP00000506669.1	O95907
SLC16A8	ENST00000320521.10 link	c.1016G>A	p.Arg339His	missense_variant	Exon 4 of 5	1		ENSP00000321735.5	O95907
SLC16A8	ENST00000469516.5 link	n.107-2318G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000477

AC:

AN:

209850

Hom.:

AF XY:

0.00000858

AC XY:

AN XY:

116604

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:

0.0000349

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1444310

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

718302

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1016G>A (p.R339H) alteration is located in exon 4 (coding exon 3) of the SLC16A8 gene. This alteration results from a G to A substitution at nucleotide position 1016, causing the arginine (R) at amino acid position 339 to be replaced by a histidine (H). 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

0.089

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

0.063

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.0

REVEL

Benign

0.25

Sift

Benign

0.043

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.24

MutPred

0.63

Loss of methylation at R339 (P = 0.0121);

MVP

0.70

MPC

0.73

ClinPred

0.70

GERP RS

3.2

Varity_R

0.12

gMVP

0.54

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