chr17-7042413-C-G

Variant names:

• chr17-7042413-C-G
• rs865782605
• NM_001370549.1:c.697G>C

Variant summary

Our verdict is Likely pathogenic. The variant received 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
• Publications: 0 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370549.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A11	NM_001370549.1	MANE Select	c.697G>C	p.Gly233Arg	missense	Exon 4 of 5	NP_001357478.1	I3L431
	SLC16A11	NM_153357.3		c.697G>C	p.Gly233Arg	missense	Exon 3 of 4	NP_699188.2	I3L431
	SLC16A11	NM_001370553.1		c.697G>C	p.Gly233Arg	missense	Exon 4 of 4	NP_001357482.1	A0A669KBK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC16A11	ENST00000574600.3	TSL:3 MANE Select	c.697G>C	p.Gly233Arg	missense	Exon 4 of 5	ENSP00000460927.2	I3L431
	SLC16A11	ENST00000573338.1	TSL:1	n.678-505G>C		intron	N/A
	SLC16A11	ENST00000662352.3		c.697G>C	p.Gly233Arg	missense	Exon 3 of 4	ENSP00000499634.1	I3L431

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

African (AFR) AF: 0.00 AC: 0 AN: 32078

American (AMR) AF: 0.00 AC: 0 AN: 37110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 36564

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1083370

Other (OTH) AF: 0.00 AC: 0 AN: 58326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Uncertain	0.093	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.023	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0020	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
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs865782605; hg19: chr17-6945732;