Genetic Variant NM_080628.3:c.337G>C (chr20-36879188-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_080628.3(TLDC2):c.337G>C(p.Gly113Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000261 in 1,612,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TLDC2
NM_080628.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

TLDC2 (HGNC:16112): (TBC/LysM-associated domain containing 2) Predicted to be involved in response to oxidative stress. Predicted to act upstream of or within negative regulation of oxidative stress-induced neuron death. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TLDC2 links:

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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=0.39535552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLDC2	NM_080628.3 link	c.337G>C	p.Gly113Arg	missense_variant	Exon 3 of 7	ENST00000217320.8	NP_542195.1	A0PJX2
TLDC2	NM_001304783.1 link	c.337G>C	p.Gly113Arg	missense_variant	Exon 3 of 6		NP_001291712.1	A0PJX2
TLDC2	XM_017027674.2 link	c.49G>C	p.Gly17Arg	missense_variant	Exon 2 of 5		XP_016883163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLDC2	ENST00000217320.8 link	c.337G>C	p.Gly113Arg	missense_variant	Exon 3 of 7	1	NM_080628.3	ENSP00000217320.3		A0PJX2
TLDC2	ENST00000602922.5 link	c.337G>C	p.Gly113Arg	missense_variant	Exon 3 of 6	1		ENSP00000473323.1		A0PJX2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

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:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000764

AC:

AN:

248632

Hom.:

AF XY:

0.0000817

AC XY:

AN XY:

134596

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:

0.000523

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000260

AC:

AN:

1459970

Hom.:

Cov.:

AF XY:

0.0000372

AC XY:

AN XY:

726272

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:

0.000394

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74364

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:

0.000620

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000836

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;T

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.40

T;T

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

3.3

M;M

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.8

.;D

REVEL

Benign

0.28

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.050

T;T

Polyphen

1.0

D;D

Vest4

0.41

MutPred

0.66

Gain of solvent accessibility (P = 0.0306);Gain of solvent accessibility (P = 0.0306);

MVP

0.76

MPC

0.16

ClinPred

0.95

GERP RS

5.1

Varity_R

0.75

gMVP

0.51

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over