Variant 17-55720976-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018286.3(TMEM100):c.95C>T(p.Thr32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM100
NM_018286.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2653123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM100	NM_018286.3 link	c.95C>T	p.Thr32Ile	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 link	c.95C>T	p.Thr32Ile	missense_variant	2/2	1	NM_018286.3	ENSP00000395328.2	Q9NV29
TMEM100	ENST00000575734.5 link	c.95C>T	p.Thr32Ile	missense_variant	4/4	2		ENSP00000465638.1	Q9NV29
TMEM100	ENST00000571679.1 link	c.95C>T	p.Thr32Ile	missense_variant	2/2	3		ENSP00000459290.1	A0A0A0MTR3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Oct 19, 2024

The c.95C>T (p.T32I) alteration is located in exon 4 (coding exon 1) of the TMEM100 gene. This alteration results from a C to T substitution at nucleotide position 95, causing the threonine (T) at amino acid position 32 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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T;T

Eigen

Benign

-0.095

Eigen_PC

Benign

0.020

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.68

.;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.8

N;.;.

REVEL

Benign

0.18

Sift

Benign

0.077

T;.;.

Sift4G

Benign

0.21

T;T;.

Polyphen

0.27

B;B;.

Vest4

0.051

MutPred

0.41

Loss of glycosylation at T32 (P = 0.0028);Loss of glycosylation at T32 (P = 0.0028);Loss of glycosylation at T32 (P = 0.0028);

MVP

0.16

MPC

0.47

ClinPred

0.58

GERP RS

3.9

Varity_R

0.068

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