Variant 7-19772651-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363562.2(TMEM196):c.46G>C(p.Val16Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000324 in 1,544,064 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM196
NM_001363562.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.50

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]

TMEM196 links:

LOC107986774 (HGNC:):

LOC107986774 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25658906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM196	NM_001363562.2 linkuse as main transcript	c.46G>C	p.Val16Leu	missense_variant	1/5	ENST00000405844.6
LOC107986774	XR_001745112.2 linkuse as main transcript	n.1126-38594C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM196	ENST00000405844.6 linkuse as main transcript	c.46G>C	p.Val16Leu	missense_variant	1/5	5	NM_001363562.2
TMEM196	ENST00000405764.7 linkuse as main transcript	c.46G>C	p.Val16Leu	missense_variant	1/4	1		P1	Q5HYL7-4
TMEM196	ENST00000422233.5 linkuse as main transcript	c.-58+916G>C		intron_variant		5
TMEM196	ENST00000493519.2 linkuse as main transcript	c.-58+451G>C		intron_variant		5			Q5HYL7-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1392010

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686456

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:

0.00000186

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Nov 14, 2023

The c.46G>C (p.V16L) alteration is located in exon 1 (coding exon 1) of the TMEM196 gene. This alteration results from a G to C substitution at nucleotide position 46, causing the valine (V) at amino acid position 16 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

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

0.087

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.017

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.2

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.16

T;T

Sift4G

Uncertain

0.034

D;D

Polyphen

0.012

.;B

Vest4

0.28

MutPred

0.26

Loss of catalytic residue at V16 (P = 0.3684);Loss of catalytic residue at V16 (P = 0.3684);

MVP

0.17

MPC

0.015

ClinPred

0.62

GERP RS

6.0

gMVP

0.76

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