Variant 17-28725339-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138463.4(TLCD1):c.325C>G(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,760 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: 0.0000075 ( 0 hom. )

Consequence

TLCD1
NM_138463.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0720

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055303752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD1	NM_138463.4 link	c.325C>G	p.Arg109Gly	missense_variant	Exon 3 of 4	ENST00000292090.8	NP_612472.1	Q96CP7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TLCD1	ENST00000292090.8 link	c.325C>G	p.Arg109Gly	missense_variant	Exon 3 of 4	1	NM_138463.4	ENSP00000292090.3	Q96CP7-1
TLCD1	ENST00000394933.7 link	c.184C>G	p.Arg62Gly	missense_variant	Exon 3 of 4	2		ENSP00000378391.3	Q96CP7-2
TLCD1	ENST00000580518.1 link	c.112C>G	p.Arg38Gly	missense_variant	Exon 3 of 4	3		ENSP00000466264.1	K7ELX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460760

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726694

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:

0.000152

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.000568

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.325C>G (p.R109G) alteration is located in exon 3 (coding exon 3) of the TLCD1 gene. This alteration results from a C to G substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a glycine (G). 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

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

D;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.82

T;T;T

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Uncertain

-0.13

MutationAssessor

Benign

1.8

L;.;.

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.2

D;D;.

REVEL

Uncertain

0.36

Sift

Benign

0.036

D;D;.

Sift4G

Uncertain

0.0070

D;D;.

Polyphen

0.97

D;.;.

Vest4

0.29

MVP

0.33

MPC

0.56

ClinPred

0.11

GERP RS

-6.3

Varity_R

0.14

gMVP

0.53

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