NM_080628.3:c.294G>C

Variant names:

• chr20-36879145-G-C
• rs150132663
• NM_080628.3:c.294G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_080628.3(TLDC2):​c.294G>C​(p.Glu98Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00462 in 1,614,052 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0048 (30 hom.)
• Consequence: TLDC2 NM_080628.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007662058).
• BP6: Variant 20-36879145-G-C is Benign according to our data. Variant chr20-36879145-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2652302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 30 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080628.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLDC2	NM_080628.3	MANE Select	c.294G>C	p.Glu98Asp	missense	Exon 3 of 7	NP_542195.1	A0PJX2
	TLDC2	NM_001304783.1		c.294G>C	p.Glu98Asp	missense	Exon 3 of 6	NP_001291712.1	A0PJX2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLDC2	ENST00000217320.8	TSL:1 MANE Select	c.294G>C	p.Glu98Asp	missense	Exon 3 of 7	ENSP00000217320.3	A0PJX2
	TLDC2	ENST00000602922.5	TSL:1	c.294G>C	p.Glu98Asp	missense	Exon 3 of 6	ENSP00000473323.1	A0PJX2
	TLDC2	ENST00000866646.1		c.294G>C	p.Glu98Asp	missense	Exon 3 of 7	ENSP00000536705.1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 464 AN: 152190 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00531

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00274 AC: 688 AN: 251174 AF XY: 0.00267

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.000897

Gnomad ASJ exome AF: 0.00367

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00158

Gnomad NFE exome AF: 0.00456

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00479 AC: 6995 AN: 1461744 Hom.: 30 Cov.: 34 AF XY: 0.00472 AC XY: 3433 AN XY: 727164

African (AFR) AF: 0.000687 AC: 23 AN: 33480

American (AMR) AF: 0.000850 AC: 38 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00344 AC: 90 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000719 AC: 62 AN: 86256

European-Finnish (FIN) AF: 0.00193 AC: 103 AN: 53288

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.00578 AC: 6422 AN: 1111998

Other (OTH) AF: 0.00404 AC: 244 AN: 60396

GnomAD4 genome AF: 0.00305 AC: 464 AN: 152308 Hom.: 1 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74458

African (AFR) AF: 0.00111 AC: 46 AN: 41574

American (AMR) AF: 0.00111 AC: 17 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00531 AC: 361 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00475 Hom.: 2

Bravo AF: 0.00266

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00727 AC: 28

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00500 AC: 43

ExAC AF: 0.00282 AC: 343

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00456

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.0077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.041
Sift	Benign	0.23	T
Sift4G	Benign	0.45	T
Polyphen		0.46	P
Vest4		0.28
MutPred		0.34		Gain of phosphorylation at Y94 (P = 0.164)
MVP		0.29
MPC		0.053
ClinPred		0.012	T
GERP RS		0.78
Varity_R		0.13
gMVP		0.22
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs150132663; hg19: chr20-35507548;