1-179637022-T-C

Position:

• chr1-179637022-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRD5	NM_001199085.3	c.1520+1135T>C		intron_variant		ENST00000444136.6	NP_001186014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRD5	ENST00000444136.6	c.1520+1135T>C		intron_variant		1	NM_001199085.3	ENSP00000406052.1
TDRD5	ENST00000294848.12	c.1520+1135T>C		intron_variant		1		ENSP00000294848.8
TDRD5	ENST00000367614.5	c.1520+1135T>C		intron_variant		2		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

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.451

Alfa AF: 0.450 Hom.: 14810

Bravo AF: 0.439

Asia WGS AF: 0.449 AC: 1561 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs10494522; hg19: chr1-179606157;