22-38081022-C-G

Variant names:

• chr22-38081022-C-G
• rs1461436003
• NM_013356.3:c.1016G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_013356.3(SLC16A8):​c.1016G>C​(p.Arg339Pro) 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 1,444,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R339H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

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.1016G>C	p.Arg339Pro	missense	Exon 5 of 6	NP_037488.2	O95907
	SLC16A8	NM_001394131.1		c.-80-2318G>C		intron	N/A	NP_001381060.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A8	ENST00000681075.2	MANE Select	c.1016G>C	p.Arg339Pro	missense	Exon 5 of 6	ENSP00000506669.1	O95907
	SLC16A8	ENST00000320521.10	TSL:1	c.1016G>C	p.Arg339Pro	missense	Exon 4 of 5	ENSP00000321735.5	O95907
	SLC16A8	ENST00000902580.1		c.1016G>C	p.Arg339Pro	missense	Exon 4 of 5	ENSP00000572639.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444312 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718304

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 43482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25874

East Asian (EAS) AF: 0.00 AC: 0 AN: 39376

South Asian (SAS) AF: 0.00 AC: 0 AN: 84888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109298

Other (OTH) AF: 0.00 AC: 0 AN: 59984

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.056
Eigen_PC	Benign	-0.025
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.43	T
M_CAP	Uncertain	0.27	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.31
Sift	Benign	0.044	D
Sift4G	Benign	0.13	T
Polyphen		0.97	D
Vest4		0.67
MutPred		0.71		Loss of methylation at R339 (P = 0.0121)
MVP		0.66
MPC		0.76
ClinPred		0.91	D
GERP RS		3.2
Varity_R		0.57
gMVP		0.83
Mutation Taster		=64/36	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: rs1461436003; hg19: chr22-38477029;