13-60429729-T-C

Variant names:

• chr13-60429729-T-C
• rs4886229
• NM_001146070.2:c.42-9959T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146070.2(TDRD3):​c.42-9959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,982 control chromosomes in the GnomAD database, including 17,754 homozygotes. 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 0.48 (17754 hom., cov: 32)
• Consequence: TDRD3 NM_001146070.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.437
• Publications: 1 publications found

Genes affected

TDRD3 (HGNC:20612): (tudor domain containing 3) Enables chromatin binding activity; methylated histone binding activity; and transcription coactivator activity. Predicted to be involved in chromatin organization and positive regulation of transcription, DNA-templated. Located in Golgi apparatus; cytosol; and nucleoplasm. Colocalizes with exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

LOC124903178 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146070.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD3	NM_001146070.2	MANE Select	c.42-9959T>C		intron	N/A	NP_001139542.1
	TDRD3	NM_001146071.1		c.-234-9959T>C		intron	N/A	NP_001139543.1
	TDRD3	NM_030794.2		c.-234-9959T>C		intron	N/A	NP_110421.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD3	ENST00000377881.8	TSL:1 MANE Select	c.42-9959T>C		intron	N/A	ENSP00000367113.2
	TDRD3	ENST00000196169.7	TSL:1	c.-234-9959T>C		intron	N/A	ENSP00000196169.3
	TDRD3	ENST00000377894.6	TSL:2	c.-234-9959T>C		intron	N/A	ENSP00000367126.2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72455 AN: 151864 Hom.: 17729 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.461

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.477 AC: 72521 AN: 151982 Hom.: 17754 Cov.: 32 AF XY: 0.479 AC XY: 35611 AN XY: 74314

African (AFR) AF: 0.418 AC: 17333 AN: 41492

American (AMR) AF: 0.545 AC: 8307 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1453 AN: 5170

South Asian (SAS) AF: 0.549 AC: 2640 AN: 4812

European-Finnish (FIN) AF: 0.519 AC: 5490 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33782 AN: 67896

Other (OTH) AF: 0.455 AC: 959 AN: 2110

Alfa AF: 0.462 Hom.: 5687

Bravo AF: 0.472

Asia WGS AF: 0.415 AC: 1438 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.7
DANN	Benign	0.86
PhyloP100		-0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs4886229; hg19: chr13-61003863;