17-7042349-C-T

Variant names:

• chr17-7042349-C-T
• rs1442055165
• NM_001370549.1:c.761G>A

Variant summary

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

The NM_001370549.1(SLC16A11):​c.761G>A​(p.Gly254Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,406,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G254R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.328

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08324942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A11	NM_001370549.1	c.761G>A	p.Gly254Glu	missense_variant	Exon 4 of 5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3	c.761G>A	p.Gly254Glu	missense_variant	Exon 3 of 4		NP_699188.2
SLC16A11	NM_001370553.1	c.761G>A	p.Gly254Glu	missense_variant	Exon 4 of 4		NP_001357482.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A11	ENST00000574600.3	c.761G>A	p.Gly254Glu	missense_variant	Exon 4 of 5	3	NM_001370549.1	ENSP00000460927.2
SLC16A11	ENST00000573338.1	n.678-441G>A		intron_variant	Intron 1 of 1	1
SLC16A11	ENST00000662352.3	c.761G>A	p.Gly254Glu	missense_variant	Exon 3 of 4			ENSP00000499634.1
SLC16A11	ENST00000673828.2	c.761G>A	p.Gly254Glu	missense_variant	Exon 4 of 4			ENSP00000501313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1406422 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 694270

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.833G>A (p.G278E) alteration is located in exon 3 (coding exon 3) of the SLC16A11 gene. This alteration results from a G to A substitution at nucleotide position 833, causing the glycine (G) at amino acid position 278 to be replaced by a glutamic acid (E). 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	0.090
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.66	N;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	1.3	N;N
REVEL	Benign	0.21
Sift	Benign	0.63	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.38	B;.
Vest4		0.20
MutPred		0.60		Gain of stability (P = 0.0553);.;
MVP		0.37
MPC		1.2
ClinPred		0.23	T
GERP RS		5.0
Varity_R		0.15
gMVP		0.51

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: rs1442055165; hg19: chr17-6945668;