Variant 12-94582133-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000261226.9(TMCC3):c.484G>A(p.Asp162Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000889 in 1,461,892 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: not found (cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TMCC3
ENST00000261226.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.62

Variant links:

Genes affected

TMCC3 (HGNC:29199): (transmembrane and coiled-coil domain family 3) Enables 14-3-3 protein binding activity and identical protein binding activity. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TMCC3 links:

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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=0.19044518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMCC3	NM_020698.4 linkuse as main transcript	c.484G>A	p.Asp162Asn	missense_variant	2/4	ENST00000261226.9	NP_065749.3	Q9ULS5
TMCC3	NM_001301036.2 linkuse as main transcript	c.391G>A	p.Asp131Asn	missense_variant	2/4		NP_001287965.1	Q9ULS5G3V207

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMCC3	ENST00000261226.9 linkuse as main transcript	c.484G>A	p.Asp162Asn	missense_variant	2/4	1	NM_020698.4	ENSP00000261226.4	Q9ULS5
TMCC3	ENST00000551457.1 linkuse as main transcript	c.391G>A	p.Asp131Asn	missense_variant	2/4	1		ENSP00000449888.1	G3V207
TMCC3	ENST00000548918.1 linkuse as main transcript	c.391G>A	p.Asp131Asn	missense_variant	2/2	2		ENSP00000450078.1	F8VQF2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251408

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000138

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:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000412

AC:

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

Feb 10, 2022

The c.484G>A (p.D162N) alteration is located in exon 2 (coding exon 2) of the TMCC3 gene. This alteration results from a G to A substitution at nucleotide position 484, causing the aspartic acid (D) at amino acid position 162 to be replaced by an asparagine (N). 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

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.;T

Eigen

Benign

0.048

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

D;D;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Benign

0.095

Sift

Uncertain

0.0010

D;D;D

Sift4G

Benign

0.10

T;T;.

Polyphen

0.014

B;.;.

Vest4

0.42

MutPred

0.43

Loss of ubiquitination at K157 (P = 0.0298);.;.;

MVP

0.12

MPC

0.69

ClinPred

0.61

GERP RS

4.4

Varity_R

0.41

gMVP

0.099

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