Variant chr11-120329989-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001198671.2(TLCD5):c.212C>T(p.Thr71Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000518 in 1,613,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 0 hom. )

Consequence

TLCD5
NM_001198671.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.81

Variant links:

Genes affected

TLCD5 (HGNC:28280): (TLC domain containing 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TLCD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TLCD5	NM_001198671.2 linkuse as main transcript	c.212C>T	p.Thr71Ile	missense_variant	3/3	ENST00000375095.3	NP_001185600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TLCD5	ENST00000375095.3 linkuse as main transcript	c.212C>T	p.Thr71Ile	missense_variant	3/3	2	NM_001198671.2	ENSP00000364236	P1	Q6ZRR5-1
TLCD5	ENST00000529187.1 linkuse as main transcript	c.278C>T	p.Thr93Ile	missense_variant	3/4	1		ENSP00000434862		Q6ZRR5-4
TLCD5	ENST00000314475.6 linkuse as main transcript	c.278C>T	p.Thr93Ile	missense_variant	3/3	2		ENSP00000312672		Q6ZRR5-3
TLCD5	ENST00000531346.1 linkuse as main transcript	n.86C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000420

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000750

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000355

AC:

AN:

250422

Hom.:

AF XY:

0.000340

AC XY:

AN XY:

135254

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000297

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000556

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000529

AC:

772

AN:

1460716

Hom.:

Cov.:

AF XY:

0.000548

AC XY:

398

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000268

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000623

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000420

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000656

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000305

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000771

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

Jul 20, 2021

The c.278C>T (p.T93I) alteration is located in exon 3 (coding exon 2) of the TMEM136 gene. This alteration results from a C to T substitution at nucleotide position 278, causing the threonine (T) at amino acid position 93 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

Pathogenic

0.83

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.41

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

D;.;.

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Uncertain

0.71

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-4.7

D;D;D

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.89

MVP

0.85

MPC

0.47

ClinPred

0.23

GERP RS

6.1

Varity_R

0.67

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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