chr17-7042413-C-G

Variant names:

• chr17-7042413-C-G
• NM_001370549.1:c.697G>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001370549.1(SLC16A11):​c.697G>C​(p.Gly233Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,407,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SLC16A11 NM_001370549.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A11	NM_001370549.1	c.697G>C	p.Gly233Arg	missense_variant	Exon 4 of 5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3	c.697G>C	p.Gly233Arg	missense_variant	Exon 3 of 4		NP_699188.2
SLC16A11	NM_001370553.1	c.697G>C	p.Gly233Arg	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.697G>C	p.Gly233Arg	missense_variant	Exon 4 of 5	3	NM_001370549.1	ENSP00000460927.2
SLC16A11	ENST00000573338.1	n.678-505G>C		intron_variant	Intron 1 of 1	1
SLC16A11	ENST00000662352.3	c.697G>C	p.Gly233Arg	missense_variant	Exon 3 of 4			ENSP00000499634.1
SLC16A11	ENST00000673828.2	c.697G>C	p.Gly233Arg	missense_variant	Exon 4 of 4			ENSP00000501313.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407640 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 695232

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: 0.0000125

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T;T
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Uncertain	-0.023	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.3	D;D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.89
MutPred		0.83		Gain of methylation at G257 (P = 0.0131);.;
MVP		0.80
MPC		0.52
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.96
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr17-6945732;