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GeneBe

7-19772606-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001363562.2(TMEM196):c.91G>A(p.Val31Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,547,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

TMEM196
NM_001363562.2 missense

Scores

1
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51
Variant links:
Genes affected
TMEM196 (HGNC:22431): (transmembrane protein 196) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02404821).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TMEM196NM_001363562.2 linkuse as main transcriptc.91G>A p.Val31Ile missense_variant 1/5 ENST00000405844.6
LOC107986774XR_001745112.2 linkuse as main transcriptn.1126-38639C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TMEM196ENST00000405844.6 linkuse as main transcriptc.91G>A p.Val31Ile missense_variant 1/55 NM_001363562.2
TMEM196ENST00000405764.7 linkuse as main transcriptc.91G>A p.Val31Ile missense_variant 1/41 P1Q5HYL7-4
TMEM196ENST00000422233.5 linkuse as main transcriptc.-58+961G>A intron_variant 5
TMEM196ENST00000493519.2 linkuse as main transcriptc.-58+496G>A intron_variant 5 Q5HYL7-2

Frequencies

GnomAD3 genomes
AF:
0.000559
AC:
85
AN:
151924
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00198
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
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:
0.00
GnomAD3 exomes
AF:
0.000160
AC:
24
AN:
150110
Hom.:
0
AF XY:
0.000113
AC XY:
9
AN XY:
79822
show subpopulations
Gnomad AFR exome
AF:
0.00269
Gnomad AMR exome
AF:
0.000127
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:
0.0000702
AC:
98
AN:
1395122
Hom.:
0
Cov.:
31
AF XY:
0.0000610
AC XY:
42
AN XY:
688082
show subpopulations
Gnomad4 AFR exome
AF:
0.00242
Gnomad4 AMR exome
AF:
0.000113
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000127
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.28e-7
Gnomad4 OTH exome
AF:
0.000277
GnomAD4 genome
AF:
0.000559
AC:
85
AN:
152042
Hom.:
0
Cov.:
31
AF XY:
0.000592
AC XY:
44
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.00198
Gnomad4 AMR
AF:
0.000196
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:
0.00
Alfa
AF:
0.000275
Hom.:
0
Bravo
AF:
0.000544
ExAC
AF:
0.000203
AC:
5

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 submitterclinical testingAmbry GeneticsNov 09, 2021The c.91G>A (p.V31I) alteration is located in exon 1 (coding exon 1) of the TMEM196 gene. This alteration results from a G to A substitution at nucleotide position 91, causing the valine (V) at amino acid position 31 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
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.14
Cadd
Uncertain
25
Dann
Uncertain
1.0
Eigen
Uncertain
0.57
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.024
T;T
MetaSVM
Benign
-0.75
T
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.15
N;N
REVEL
Benign
0.21
Sift
Benign
0.21
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.90
.;P
Vest4
0.48
MVP
0.21
MPC
0.013
ClinPred
0.089
T
GERP RS
6.0
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.

Other links and lift over

dbSNP: rs574384459; hg19: chr7-19812229; COSMIC: COSV99066731; API