Variant 17-32931541-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000579849.6(TMEM98):c.13G>T(p.Val5Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,453,170 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TMEM98
ENST00000579849.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.29

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TMEM98	NM_015544.3 linkuse as main transcript	c.13G>T	p.Val5Leu	missense_variant	3/8	ENST00000579849.6	NP_056359.2
TMEM98	NM_001033504.2 linkuse as main transcript	c.13G>T	p.Val5Leu	missense_variant	2/7		NP_001028676.1
TMEM98	NM_001301746.2 linkuse as main transcript	c.13G>T	p.Val5Leu	missense_variant	4/9		NP_001288675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM98	ENST00000579849.6 linkuse as main transcript	c.13G>T	p.Val5Leu	missense_variant	3/8	1	NM_015544.3	ENSP00000463245	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1453170

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

721850

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.13G>T (p.V5L) alteration is located in exon 3 (coding exon 1) of the TMEM98 gene. This alteration results from a G to T substitution at nucleotide position 13, causing the valine (V) at amino acid position 5 to be replaced by a leucine (L). 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

0.96

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T;T;T;T;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;D;D;D;D;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.9

L;L;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.3

N;.;N;N;.;N;.

REVEL

Uncertain

0.40

Sift

Uncertain

0.0080

D;.;D;D;.;D;.

Sift4G

Uncertain

0.030

D;D;D;D;D;D;D

Polyphen

0.93

P;P;.;.;.;.;.

Vest4

0.88

MutPred

0.26

Loss of catalytic residue at V5 (P = 0.1009);Loss of catalytic residue at V5 (P = 0.1009);Loss of catalytic residue at V5 (P = 0.1009);Loss of catalytic residue at V5 (P = 0.1009);Loss of catalytic residue at V5 (P = 0.1009);Loss of catalytic residue at V5 (P = 0.1009);Loss of catalytic residue at V5 (P = 0.1009);

MVP

0.55

MPC

0.44

ClinPred

0.73

GERP RS

4.9

Varity_R

0.40

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.41

Position offset: 16

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