Variant 17-28725368-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_138463.4(TLCD1):c.296C>T(p.Thr99Met) variant causes a missense change. The variant allele was found at a frequency of 0.000454 in 1,614,042 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: 𝑓 0.00037 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

TLCD1
NM_138463.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

TLCD1 (HGNC:25177): (TLC domain containing 1) Involved in several processes, including membrane assembly; phospholipid homeostasis; and regulation of membrane lipid distribution. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TLCD1 links:

Genome browser will be placed here

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=0.2871316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLCD1	NM_138463.4 linkuse as main transcript	c.296C>T	p.Thr99Met	missense_variant	3/4	ENST00000292090.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLCD1	ENST00000292090.8 linkuse as main transcript	c.296C>T	p.Thr99Met	missense_variant	3/4	1	NM_138463.4	P1	Q96CP7-1
TLCD1	ENST00000394933.7 linkuse as main transcript	c.155C>T	p.Thr52Met	missense_variant	3/4	2			Q96CP7-2
TLCD1	ENST00000580518.1 linkuse as main transcript	c.83C>T	p.Thr28Met	missense_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000764

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000266

AC:

AN:

251468

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000571

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000463

AC:

677

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

326

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000593

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000368

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000764

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000608

Hom.:

Bravo

AF:

0.000363

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000415

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.296C>T (p.T99M) alteration is located in exon 3 (coding exon 3) of the TLCD1 gene. This alteration results from a C to T substitution at nucleotide position 296, causing the threonine (T) at amino acid position 99 to be replaced by a methionine (M). 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

0.22

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.11

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Uncertain

0.094

MutationAssessor

Benign

0.69

N;.;.

MutationTaster

Benign

0.93

D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.1

N;N;.

REVEL

Uncertain

0.33

Sift

Benign

0.046

D;D;.

Sift4G

Uncertain

0.0030

D;D;.

Polyphen

0.70

P;.;.

Vest4

0.57

MVP

0.65

MPC

0.62

ClinPred

0.36

GERP RS

5.6

Varity_R

0.12

gMVP

0.56

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