NM_001146070.2:c.2118+4372G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146070.2(TDRD3):​c.2118+4372G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,214 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 0.0000066 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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>C		intron	N/A	NP_001139542.1
	TDRD3	NM_001146071.1		c.1839+4372G>C		intron	N/A	NP_001139543.1
	TDRD3	NM_030794.2		c.1839+4372G>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.2118+4372G>C		intron	N/A	ENSP00000367113.2
	TDRD3	ENST00000196169.7	TSL:1	c.1839+4372G>C		intron	N/A	ENSP00000196169.3
	TDRD3	ENST00000621840.4	TSL:1	c.1836+4372G>C		intron	N/A	ENSP00000477993.1

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151214 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73838

African (AFR) AF: 0.00 AC: 0 AN: 41224

American (AMR) AF: 0.00 AC: 0 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67712

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 10700

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		0.75

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;