2-62506062-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_198276.3(TMEM17):c.68A>T(p.Asn23Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,611,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

TMEM17
NM_198276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0380

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity TMM17_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07397571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TMEM17	NM_198276.3 linkuse as main transcript	c.68A>T	p.Asn23Ile	missense_variant	1/4	ENST00000335390.6
TMEM17	XM_024452749.2 linkuse as main transcript	c.68A>T	p.Asn23Ile	missense_variant	1/6
TMEM17	XM_011532693.3 linkuse as main transcript	c.68A>T	p.Asn23Ile	missense_variant	1/4
TMEM17	XM_011532694.3 linkuse as main transcript	c.68A>T	p.Asn23Ile	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TMEM17	ENST00000335390.6 linkuse as main transcript	c.68A>T	p.Asn23Ile	missense_variant	1/4	1	NM_198276.3	P1
TMEM17	ENST00000494919.1 linkuse as main transcript	n.408A>T		non_coding_transcript_exon_variant	1/3	2
TMEM17	ENST00000479763.5 linkuse as main transcript	n.109-3268A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000478

GnomAD3 exomes

AF:

0.0000285

AC:

AN:

245786

Hom.:

AF XY:

0.00000750

AC XY:

AN XY:

133338

show subpopulations

Gnomad AFR exome

AF:

0.000391

Gnomad AMR exome

AF:

0.0000295

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:

0.0000192

AC:

AN:

1458694

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725554

show subpopulations

Gnomad4 AFR exome

AF:

0.000544

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000350

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.000177

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000327

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:

0.000473

Bravo

AF:

0.000238

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.68A>T (p.N23I) alteration is located in exon 1 (coding exon 1) of the TMEM17 gene. This alteration results from a A to T substitution at nucleotide position 68, causing the asparagine (N) at amino acid position 23 to be replaced by an isoleucine (I). 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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.045

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.66

M_CAP

Benign

0.017

MetaRNN

Benign

0.074

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.97

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.067

Sift

Benign

0.054

Sift4G

Benign

0.091

Polyphen

0.0050

Vest4

0.24

MutPred

0.11

Loss of disorder (P = 0.1101);

MVP

0.57

MPC

0.30

ClinPred

0.057

GERP RS

-1.7

Varity_R

0.15

gMVP

0.62

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