17-7042427-G-C

Position:

• chr17-7042427-G-C

Variant summary

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

The NM_001370549.1(SLC16A11):​c.683C>G​(p.Ala228Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.40

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=0.4229932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A11	NM_001370549.1	c.683C>G	p.Ala228Gly	missense_variant	4/5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3	c.683C>G	p.Ala228Gly	missense_variant	3/4		NP_699188.2
SLC16A11	NM_001370553.1	c.683C>G	p.Ala228Gly	missense_variant	4/4		NP_001357482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC16A11	ENST00000574600.3	c.683C>G	p.Ala228Gly	missense_variant	4/5	3	NM_001370549.1	ENSP00000460927	P1
SLC16A11	ENST00000573338.1	n.677+503C>G		intron_variant, non_coding_transcript_variant		1
SLC16A11	ENST00000662352.3	c.683C>G	p.Ala228Gly	missense_variant	3/4			ENSP00000499634	P1
SLC16A11	ENST00000673828.2	c.683C>G	p.Ala228Gly	missense_variant	4/4			ENSP00000501313

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2021

The c.755C>G (p.A252G) alteration is located in exon 3 (coding exon 3) of the SLC16A11 gene. This alteration results from a C to G substitution at nucleotide position 755, causing the alanine (A) at amino acid position 252 to be replaced by a glycine (G). 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	0.16
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.17	T;T
Polyphen		0.80	P;.
Vest4		0.26
MutPred		0.73		Loss of stability (P = 0.0206);.;
MVP		0.60
MPC		0.86
ClinPred		0.79	D
GERP RS		4.3
Varity_R		0.32
gMVP		0.39

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: chr17-6945746;