chr13-60539605-G-A

Variant names:

• chr13-60539605-G-A
• rs4886238
• NM_001146070.2:c.2118+4372G>A

Variant summary

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

The NM_001146070.2(TDRD3):​c.2118+4372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,232 control chromosomes in the GnomAD database, including 7,512 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 0.31 (7512 hom., cov: 32)
• Consequence: TDRD3 NM_001146070.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.754
• Publications: 27 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 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.2118+4372G>A		intron	N/A	NP_001139542.1
	TDRD3	NM_001146071.1		c.1839+4372G>A		intron	N/A	NP_001139543.1
	TDRD3	NM_030794.2		c.1839+4372G>A		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.2118+4372G>A		intron	N/A	ENSP00000367113.2
	TDRD3	ENST00000196169.7	TSL:1	c.1839+4372G>A		intron	N/A	ENSP00000196169.3
	TDRD3	ENST00000621840.4	TSL:1	c.1836+4372G>A		intron	N/A	ENSP00000477993.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 46931 AN: 151118 Hom.: 7505 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.0534

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.310 AC: 46957 AN: 151232 Hom.: 7512 Cov.: 32 AF XY: 0.309 AC XY: 22864 AN XY: 73910

African (AFR) AF: 0.289 AC: 11950 AN: 41310

American (AMR) AF: 0.277 AC: 4198 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1333 AN: 3466

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1715 AN: 4796

European-Finnish (FIN) AF: 0.341 AC: 3530 AN: 10344

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22774 AN: 67670

Other (OTH) AF: 0.301 AC: 631 AN: 2098

Alfa AF: 0.312 Hom.: 10700

Bravo AF: 0.300

Asia WGS AF: 0.195 AC: 662 AN: 3394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		0.75
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: rs4886238; hg19: chr13-61113739;