Variant 17-55720902-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018286.3(TMEM100):c.169A>G(p.Ile57Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMEM100
NM_018286.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.695

Variant links:

Genes affected

TMEM100 (HGNC:25607): (transmembrane protein 100) Involved in BMP signaling pathway. Located in several cellular components, including endoplasmic reticulum; perikaryon; and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TMEM100 links:

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=0.04324615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM100	NM_018286.3 linkuse as main transcript	c.169A>G	p.Ile57Val	missense_variant	2/2	ENST00000424486.3	NP_060756.2	Q9NV29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM100	ENST00000424486.3 linkuse as main transcript	c.169A>G	p.Ile57Val	missense_variant	2/2	1	NM_018286.3	ENSP00000395328.2	Q9NV29
TMEM100	ENST00000575734.5 linkuse as main transcript	c.169A>G	p.Ile57Val	missense_variant	4/4	2		ENSP00000465638.1	Q9NV29
TMEM100	ENST00000571679.1 linkuse as main transcript	c.169A>G	p.Ile57Val	missense_variant	2/2	3		ENSP00000459290.1	A0A0A0MTR3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

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:

0.000193

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

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jan 04, 2024

The c.169A>G (p.I57V) alteration is located in exon 4 (coding exon 1) of the TMEM100 gene. This alteration results from a A to G substitution at nucleotide position 169, causing the isoleucine (I) at amino acid position 57 to be replaced by a valine (V). 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

Benign

0.063

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.2

DANN

Benign

0.81

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.61

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.043

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.85

L;L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

0.34

N;.;.

REVEL

Benign

0.049

Sift

Benign

0.96

T;.;.

Sift4G

Benign

0.74

T;T;.

Polyphen

0.0010

B;B;.

Vest4

0.026

MutPred

0.22

Loss of catalytic residue at P59 (P = 0.0396);Loss of catalytic residue at P59 (P = 0.0396);Loss of catalytic residue at P59 (P = 0.0396);

MVP

0.055

MPC

0.21

ClinPred

0.044

GERP RS

-1.9

Varity_R

0.021

gMVP

0.36

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