17-7041798-A-T

Position:

• chr17-7041798-A-T

Variant summary

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

The NM_001370549.1(SLC16A11):​c.1225T>A​(p.Cys409Ser) variant causes a missense change. 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: 3.60

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=0.29855227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC16A11	NM_001370549.1	c.1225T>A	p.Cys409Ser	missense_variant	5/5	ENST00000574600.3	NP_001357478.1
SLC16A11	NM_153357.3	c.1225T>A	p.Cys409Ser	missense_variant	4/4		NP_699188.2
SLC16A11	NM_001370553.1	c.*133T>A		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.1225T>A	p.Cys409Ser	missense_variant	5/5	3	NM_001370549.1	ENSP00000460927	P1
SLC16A11	ENST00000573338.1	n.788T>A		non_coding_transcript_exon_variant	2/2	1
SLC16A11	ENST00000662352.3	c.1225T>A	p.Cys409Ser	missense_variant	4/4			ENSP00000499634	P1
SLC16A11	ENST00000673828.2	c.*133T>A		3_prime_UTR_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

Sep 21, 2023

The c.1297T>A (p.C433S) alteration is located in exon 4 (coding exon 4) of the SLC16A11 gene. This alteration results from a T to A substitution at nucleotide position 1297, causing the cysteine (C) at amino acid position 433 to be replaced by a serine (S). 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	0.18
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0069	T;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.71	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.16
Sift	Benign	0.21	T;T
Sift4G	Benign	0.15	T;T
Polyphen		1.0	D;.
Vest4		0.49
MutPred		0.35		Gain of glycosylation at C433 (P = 0);.;
MVP		0.30
MPC		1.2
ClinPred		0.75	D
GERP RS		5.1
Varity_R		0.13
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-6945117;