chr22-38078454-G-T

Variant names:

• chr22-38078454-G-T
• rs377373294
• NM_013356.3:c.1449C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013356.3(SLC16A8):​c.1449C>A​(p.Ser483Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: SLC16A8 NM_013356.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08318186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3	c.1449C>A	p.Ser483Arg	missense_variant	Exon 6 of 6	ENST00000681075.2	NP_037488.2
SLC16A8	NM_001394131.1	c.171C>A	p.Ser57Arg	missense_variant	Exon 2 of 2		NP_001381060.1
SLC16A8	XM_017028685.2	c.1449C>A	p.Ser483Arg	missense_variant	Exon 4 of 4		XP_016884174.1
LOC105373027	XR_938249.3	n.-187G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A8	ENST00000681075.2	c.1449C>A	p.Ser483Arg	missense_variant	Exon 6 of 6		NM_013356.3	ENSP00000506669.1
SLC16A8	ENST00000320521.10	c.1449C>A	p.Ser483Arg	missense_variant	Exon 5 of 5	1		ENSP00000321735.5
SLC16A8	ENST00000469516.5	n.357C>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.00 AC: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1449C>A (p.S483R) alteration is located in exon 5 (coding exon 4) of the SLC16A8 gene. This alteration results from a C to A substitution at nucleotide position 1449, causing the serine (S) at amino acid position 483 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	Benign	0.15
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.8
DANN	Benign	0.93
DEOGEN2	Benign	0.052	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.048
Sift	Benign	0.31	T
Sift4G	Benign	0.42	T
Polyphen		0.072	B
Vest4		0.14
MutPred		0.17		Loss of phosphorylation at S483 (P = 0.0134);
MVP		0.15
MPC		0.23
ClinPred		0.089	T
GERP RS		0.95
Varity_R		0.045
gMVP		0.41

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

Other links and lift over

dbSNP: rs377373294; hg19: chr22-38474461;