rs777819488

Variant names:

• chr22-38078701-C-T
• rs777819488
• NM_013356.3:c.1202G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-38078701-C-T
• chr22-38078701-C-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013356.3(SLC16A8):​c.1202G>A​(p.Arg401His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000418 in 1,601,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R401C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.745
• Publications: 0 publications found

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]

LOC105373027 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049990296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013356.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A8	NM_013356.3	MANE Select	c.1202G>A	p.Arg401His	missense	Exon 6 of 6	NP_037488.2	O95907
	SLC16A8	NM_001394131.1		c.-77G>A		5_prime_UTR	Exon 2 of 2	NP_001381060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A8	ENST00000681075.2	MANE Select	c.1202G>A	p.Arg401His	missense	Exon 6 of 6	ENSP00000506669.1	O95907
	SLC16A8	ENST00000320521.10	TSL:1	c.1202G>A	p.Arg401His	missense	Exon 5 of 5	ENSP00000321735.5	O95907
	SLC16A8	ENST00000902580.1		c.1202G>A	p.Arg401His	missense	Exon 5 of 5	ENSP00000572639.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152206 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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

GnomAD2 exomes AF: 0.000182 AC: 45 AN: 247364 AF XY: 0.000127

Gnomad AFR exome AF: 0.000251

Gnomad AMR exome AF: 0.00116

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: 0.0000393 AC: 57 AN: 1449506 Hom.: 0 Cov.: 35 AF XY: 0.0000306 AC XY: 22 AN XY: 718096

African (AFR) AF: 0.000180 AC: 6 AN: 33276

American (AMR) AF: 0.000898 AC: 40 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26008

East Asian (EAS) AF: 0.00 AC: 0 AN: 39308

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 86010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00000545 AC: 6 AN: 1101832

Other (OTH) AF: 0.0000502 AC: 3 AN: 59798

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152324 Hom.: 0 Cov.: 34 AF XY: 0.0000671 AC XY: 5 AN XY: 74478

African (AFR) AF: 0.000120 AC: 5 AN: 41576

American (AMR) AF: 0.000261 AC: 4 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000761 Hom.: 0

Bravo AF: 0.000170

ExAC AF: 0.000148 AC: 18

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.74
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.083
Sift	Benign	0.13	T
Sift4G	Benign	0.53	T
Polyphen		0.49	P
Vest4		0.11
MVP		0.32
MPC		0.23
ClinPred		0.017	T
GERP RS		1.7
Varity_R		0.077
gMVP		0.34
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs777819488; hg19: chr22-38474708; COSMIC: COSV100260023; COSMIC: COSV100260023;