chr22-38080968-T-A

Variant names:

• chr22-38080968-T-A
• NM_013356.3:c.1070A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_013356.3(SLC16A8):​c.1070A>T​(p.Tyr357Phe) variant causes a missense change. 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: 4.98

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33539617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A8	NM_013356.3	c.1070A>T	p.Tyr357Phe	missense_variant	Exon 5 of 6	ENST00000681075.2	NP_037488.2
SLC16A8	XM_017028685.2	c.1070A>T	p.Tyr357Phe	missense_variant	Exon 3 of 4		XP_016884174.1
SLC16A8	NM_001394131.1	c.-80-2264A>T		intron_variant	Intron 1 of 1		NP_001381060.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A8	ENST00000681075.2	c.1070A>T	p.Tyr357Phe	missense_variant	Exon 5 of 6		NM_013356.3	ENSP00000506669.1
SLC16A8	ENST00000320521.10	c.1070A>T	p.Tyr357Phe	missense_variant	Exon 4 of 5	1		ENSP00000321735.5
SLC16A8	ENST00000469516.5	n.107-2264A>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 31, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1070A>T (p.Y357F) alteration is located in exon 4 (coding exon 3) of the SLC16A8 gene. This alteration results from a A to T substitution at nucleotide position 1070, causing the tyrosine (Y) at amino acid position 357 to be replaced by a phenylalanine (F). 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	0.26
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.030	B
Vest4		0.54
MutPred		0.68		Loss of helix (P = 0.3949);
MVP		0.46
MPC		0.18
ClinPred		0.62	D
GERP RS		3.3
Varity_R		0.17
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-38476975;