Genetic Variant NM_080628.3:c.182T>A (chr20-36878047-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

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

The NM_080628.3(TLDC2):c.182T>A(p.Ile61Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TLDC2
NM_080628.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.06

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLDC2	NM_080628.3 link	c.182T>A	p.Ile61Asn	missense_variant	Exon 2 of 7	ENST00000217320.8	NP_542195.1	A0PJX2
TLDC2	NM_001304783.1 link	c.182T>A	p.Ile61Asn	missense_variant	Exon 2 of 6		NP_001291712.1	A0PJX2
TLDC2	XM_017027674.2 link	c.-102T>A		5_prime_UTR_variant	Exon 1 of 5		XP_016883163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLDC2	ENST00000217320.8 link	c.182T>A	p.Ile61Asn	missense_variant	Exon 2 of 7	1	NM_080628.3	ENSP00000217320.3		A0PJX2
TLDC2	ENST00000602922.5 link	c.182T>A	p.Ile61Asn	missense_variant	Exon 2 of 6	1		ENSP00000473323.1		A0PJX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726608

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:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

T;T

Eigen

Benign

0.060

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.5

M;M

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.6

.;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

.;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.74

P;P

Vest4

0.88

MutPred

0.58

Gain of disorder (P = 0.0208);Gain of disorder (P = 0.0208);

MVP

0.45

MPC

0.24

ClinPred

0.97

GERP RS

3.6

Varity_R

0.57

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over