chr2-62502779-G-A

Position:

• chr2-62502779-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198276.3(TMEM17):​c.116C>T​(p.Ser39Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM17 NM_198276.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.44

Genes affected

TMEM17 (HGNC:26623): (transmembrane protein 17) Involved in non-motile cilium assembly. Predicted to be located in ciliary membrane. Predicted to be part of MKS complex. Predicted to be active in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

TMEM17 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM17	NM_198276.3	c.116C>T	p.Ser39Phe	missense_variant	2/4	ENST00000335390.6	NP_938017.2
TMEM17	XM_024452749.2	c.116C>T	p.Ser39Phe	missense_variant	2/6		XP_024308517.1
TMEM17	XM_011532693.3	c.116C>T	p.Ser39Phe	missense_variant	2/4		XP_011530995.1
TMEM17	XM_011532694.3	c.116C>T	p.Ser39Phe	missense_variant	2/5		XP_011530996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM17	ENST00000335390.6	c.116C>T	p.Ser39Phe	missense_variant	2/4	1	NM_198276.3	ENSP00000335094.5
TMEM17	ENST00000479763.5	n.124C>T		non_coding_transcript_exon_variant	2/3	5
TMEM17	ENST00000494919.1	n.456C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jun 22, 2023

The c.116C>T (p.S39F) alteration is located in exon 2 (coding exon 2) of the TMEM17 gene. This alteration results from a C to T substitution at nucleotide position 116, causing the serine (S) at amino acid position 39 to be replaced by a phenylalanine (F). 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	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.45		Loss of disorder (P = 0.0036);
MVP		0.91
MPC		0.83
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.74
gMVP		0.96

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: chr2-62729914;