1-179637022-T-C

Variant names:

• chr1-179637022-T-C
• rs10494522
• NM_001199085.3:c.1520+1135T>C

Variant summary

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

The NM_001199085.3(TDRD5):​c.1520+1135T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,122 control chromosomes in the GnomAD database, including 14,654 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 0.44 (14654 hom., cov: 33)
• Consequence: TDRD5 NM_001199085.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 4 publications found

Genes affected

TDRD5 (HGNC:20614): (tudor domain containing 5) Predicted to be involved in DNA methylation involved in gamete generation; P granule organization; and spermatid development. Predicted to be located in chromatoid body and pi-body. [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 (AMR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199085.3. 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
	TDRD5	NM_001199085.3	MANE Select	c.1520+1135T>C		intron	N/A	NP_001186014.1
	TDRD5	NM_001199089.3		c.1520+1135T>C		intron	N/A	NP_001186018.1
	TDRD5	NM_001199091.2		c.1520+1135T>C		intron	N/A	NP_001186020.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD5	ENST00000444136.6	TSL:1 MANE Select	c.1520+1135T>C		intron	N/A	ENSP00000406052.1
	TDRD5	ENST00000294848.12	TSL:1	c.1520+1135T>C		intron	N/A	ENSP00000294848.8
	TDRD5	ENST00000367614.5	TSL:2	c.1520+1135T>C		intron	N/A	ENSP00000356586.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66521 AN: 152002 Hom.: 14626 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.438 AC: 66601 AN: 152122 Hom.: 14654 Cov.: 33 AF XY: 0.436 AC XY: 32466 AN XY: 74382

African (AFR) AF: 0.380 AC: 15775 AN: 41514

American (AMR) AF: 0.473 AC: 7227 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2426 AN: 5172

South Asian (SAS) AF: 0.414 AC: 1998 AN: 4822

European-Finnish (FIN) AF: 0.467 AC: 4936 AN: 10574

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31370 AN: 67982

Other (OTH) AF: 0.451 AC: 954 AN: 2116

Alfa AF: 0.450 Hom.: 17678

Bravo AF: 0.439

Asia WGS AF: 0.449 AC: 1561 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.79
PhyloP100		-0.70
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: rs10494522; hg19: chr1-179606157;