17-32936425-G-A

Variant summary

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

The ENST00000579849.6(TMEM98):​c.391G>A​(p.Val131Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TMEM98
ENST00000579849.6 missense

Scores

4
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.41
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM98NM_015544.3 linkuse as main transcriptc.391G>A p.Val131Met missense_variant 6/8 ENST00000579849.6 NP_056359.2
TMEM98NM_001033504.2 linkuse as main transcriptc.391G>A p.Val131Met missense_variant 5/7 NP_001028676.1
TMEM98NM_001301746.2 linkuse as main transcriptc.391G>A p.Val131Met missense_variant 7/9 NP_001288675.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM98ENST00000579849.6 linkuse as main transcriptc.391G>A p.Val131Met missense_variant 6/81 NM_015544.3 ENSP00000463245 P1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152230
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251328
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461864
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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:
0.0000225
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152230
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.000193
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJan 24, 2024The c.391G>A (p.V131M) alteration is located in exon 6 (coding exon 4) of the TMEM98 gene. This alteration results from a G to A substitution at nucleotide position 391, causing the valine (V) at amino acid position 131 to be replaced by a methionine (M). 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
0.87
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
T;T;T;T;T;T
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
.;D;D;D;D;D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.48
T;T;T;T;T;T
MetaSVM
Benign
-0.62
T
MutationAssessor
Benign
1.7
L;L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-1.2
N;.;N;N;.;N
REVEL
Uncertain
0.33
Sift
Uncertain
0.0060
D;.;D;D;.;D
Sift4G
Uncertain
0.019
D;D;D;D;D;D
Polyphen
0.99
D;D;.;.;.;.
Vest4
0.86
MVP
0.42
MPC
1.1
ClinPred
0.71
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.78

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.

Other links and lift over

dbSNP: rs763376053; hg19: chr17-31263443; API