Variant 17-32940816-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The ENST00000579849.6(TMEM98):c.504C>T(p.His168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00711 in 1,614,136 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0072 ( 52 hom. )

Consequence

TMEM98
ENST00000579849.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.107

Variant links:

Genes affected

TMEM98 (HGNC:24529): (transmembrane protein 98) This gene encodes a transmembrane protein. A missense mutation in this gene result in Nanophthalmos 4 (NNO4). Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2014]

TMEM98 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 17-32940816-C-T is Benign according to our data. Variant chr17-32940816-C-T is described in ClinVar as [Benign]. Clinvar id is 790428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.107 with no splicing effect.

BS2

High AC in GnomAd4 at 981 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM98	NM_015544.3 linkuse as main transcript	c.504C>T	p.His168=	synonymous_variant	8/8	ENST00000579849.6	NP_056359.2
TMEM98	NM_001033504.2 linkuse as main transcript	c.504C>T	p.His168=	synonymous_variant	7/7		NP_001028676.1
TMEM98	NM_001301746.2 linkuse as main transcript	c.504C>T	p.His168=	synonymous_variant	9/9		NP_001288675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM98	ENST00000579849.6 linkuse as main transcript	c.504C>T	p.His168=	synonymous_variant	8/8	1	NM_015544.3	ENSP00000463245	P1

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

981

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00850

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00607

AC:

1526

AN:

251246

Hom.:

AF XY:

0.00635

AC XY:

862

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.0114

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00759

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00718

AC:

10489

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

5142

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.0116

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.00802

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.00644

AC:

981

AN:

152320

Hom.:

Cov.:

AF XY:

0.00602

AC XY:

448

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00850

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00727

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00731

EpiControl

AF:

0.00877

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	TMEM98: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

1.1

DANN

Benign

0.57

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