Variant chr2-62502449-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198276.3(TMEM17):c.306C>A(p.Asn102Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,603,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM17
NM_198276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

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 links:

TMEM17 (HGNC:):

TMEM17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.989

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM17	NM_198276.3 linkuse as main transcript	c.306C>A	p.Asn102Lys	missense_variant	3/4	ENST00000335390.6	NP_938017.2	Q86X19
TMEM17	XM_024452749.2 linkuse as main transcript	c.306C>A	p.Asn102Lys	missense_variant	3/6		XP_024308517.1
TMEM17	XM_011532693.3 linkuse as main transcript	c.306C>A	p.Asn102Lys	missense_variant	3/4		XP_011530995.1
TMEM17	XM_011532694.3 linkuse as main transcript	c.306C>A	p.Asn102Lys	missense_variant	3/5		XP_011530996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM17	ENST00000335390.6 linkuse as main transcript	c.306C>A	p.Asn102Lys	missense_variant	3/4	1	NM_198276.3	ENSP00000335094.5	Q86X19
TMEM17	ENST00000479763.5 linkuse as main transcript	n.314C>A		non_coding_transcript_exon_variant	3/3	5
TMEM17	ENST00000494919.1 linkuse as main transcript	n.646C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250958

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135632

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451222

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722670

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Orofaciodigital syndrome I

Uncertain:1

Uncertain significance, criteria provided, single submitter

curation

SIB Swiss Institute of Bioinformatics

Apr 16, 2018

This variant is interpreted as a Uncertain Significance, for Orofaciodigital syndrome, Autosomal Recessive inheritance. The following ACMG Tag(s) were applied: PM2-Supporting => PM2 downgraded in strength to Supporting. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PS3-Moderate => PS3 downgraded in strength to Moderate (PMID:26982032). PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PMID:26982032). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.40

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.91

MutationAssessor

Pathogenic

3.3

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-6.0

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.97

MutPred

0.95

Gain of methylation at N102 (P = 0.0142);

MVP

0.97

MPC

0.88

ClinPred

1.0

GERP RS

3.2

Varity_R

0.90

gMVP

0.99

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over