Variant chr1-95191684-A-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 NM_152487.3(TLCD4):c.608A>T(p.Tyr203Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,042 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: 0.0000041 ( 0 hom. )

Consequence

TLCD4
NM_152487.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.940

Variant links:

Genes affected

TLCD4 (HGNC:26477): (TLC domain containing 4) Predicted to be involved in lipid homeostasis. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TLCD4 links:

TLCD4-RWDD3 (HGNC:):

TLCD4-RWDD3 links:

RWDD3-DT (HGNC:55839): (RWDD3 divergent transcript)

RWDD3-DT 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=0.083470166).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TLCD4	NM_152487.3 linkuse as main transcript	c.608A>T	p.Tyr203Phe	missense_variant	7/7	ENST00000370203.9
TLCD4-RWDD3	NM_001199691.1 linkuse as main transcript	c.473+17795A>T		intron_variant
RWDD3-DT	NR_125949.1 linkuse as main transcript	n.467+13412T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TLCD4	ENST00000370203.9 linkuse as main transcript	c.608A>T	p.Tyr203Phe	missense_variant	7/7	1	NM_152487.3	P1
RWDD3-DT	ENST00000663020.1 linkuse as main transcript	n.443-11325T>A		intron_variant, non_coding_transcript_variant
RWDD3-DT	ENST00000419846.1 linkuse as main transcript	n.464+13412T>A		intron_variant, non_coding_transcript_variant		3
RWDD3-DT	ENST00000421762.5 linkuse as main transcript	n.467+13412T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000159

AC:

AN:

251464

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

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:

0.000163

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

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:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Bravo

AF:

0.0000113

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 31, 2022

The c.608A>T (p.Y203F) alteration is located in exon 1 (coding exon 1) of the TMEM56 gene. This alteration results from a A to T substitution at nucleotide position 608, causing the tyrosine (Y) at amino acid position 203 to be replaced by a phenylalanine (F). 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

0.074

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.5

DANN

Benign

0.73

DEOGEN2

Benign

0.24

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.72

M_CAP

Benign

0.0063

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.30

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.33

REVEL

Benign

0.20

Sift

Benign

0.53

Sift4G

Benign

0.89

Polyphen

0.0010

Vest4

0.10

MutPred

0.55

Loss of sheet (P = 0.0181);

MVP

0.38

MPC

0.28

ClinPred

0.015

GERP RS

0.63

Varity_R

0.059

gMVP

0.30

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