rs34994431

Positions:

• chr17-7041898-C-A
• chr17-7041898-C-T

Variant summary

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

The NM_001370549.1(SLC16A11):​c.1125G>T​(p.Arg375Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

Genes affected

SLC16A11 (HGNC:23093): (solute carrier family 16 member 11) Enables pyruvate transmembrane transporter activity. Involved in lipid metabolic process. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.32991433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A11	NM_001370549.1	c.1125G>T	p.Arg375Ser	missense_variant	5/5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3	c.1125G>T	p.Arg375Ser	missense_variant	4/4		NP_699188.2
SLC16A11	NM_001370553.1	c.*33G>T		3_prime_UTR_variant	4/4		NP_001357482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A11	ENST00000574600.3	c.1125G>T	p.Arg375Ser	missense_variant	5/5	3	NM_001370549.1	ENSP00000460927	P1
SLC16A11	ENST00000573338.1	n.688G>T		non_coding_transcript_exon_variant	2/2	1
SLC16A11	ENST00000662352.3	c.1125G>T	p.Arg375Ser	missense_variant	4/4			ENSP00000499634	P1
SLC16A11	ENST00000673828.2	c.*33G>T		3_prime_UTR_variant	4/4			ENSP00000501313

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0058	T;.
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.68	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	0.54	D;D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.10
Sift	Benign	0.24	T;T
Sift4G	Uncertain	0.050	T;T
Polyphen		0.18	B;.
Vest4		0.68
MutPred		0.49		Loss of methylation at R399 (P = 0.0264);.;
MVP		0.40
MPC		0.51
ClinPred		0.33	T
GERP RS		3.0
Varity_R		0.18
gMVP		0.61

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: rs34994431; hg19: chr17-6945217;