rs17665859

Variant names:

• chr8-495601-T-C
• rs17665859
• NM_001384899.1:c.109-1004A>G

Variant summary

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

The NM_001384899.1(TDRP):​c.109-1004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,268 control chromosomes in the GnomAD database, including 369 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 0.061 (369 hom., cov: 33)
• Consequence: TDRP NM_001384899.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 6 publications found

Genes affected

TDRP (HGNC:26951): (testis development related protein) Acts upstream of or within spermatogenesis. Located in cytosol and nucleus. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TDRP	NM_001384899.1	c.109-1004A>G		intron_variant	Intron 1 of 2	ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2	c.109-1004A>G		intron_variant	Intron 1 of 3		NP_001243042.1
TDRP	NM_175075.5	c.109-1004A>G		intron_variant	Intron 2 of 3		NP_778250.2
TDRP	XM_047421392.1	c.139-1004A>G		intron_variant	Intron 2 of 3		XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11	c.109-1004A>G		intron_variant	Intron 1 of 2	1	NM_001384899.1	ENSP00000315111.6
TDRP	ENST00000523656.5	c.109-1004A>G		intron_variant	Intron 2 of 4	5		ENSP00000430325.1

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9290 AN: 152150 Hom.: 372 Cov.: 33

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0745

Gnomad OTH AF: 0.0822

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

GnomAD4 genome AF: 0.0610 AC: 9290 AN: 152268 Hom.: 369 Cov.: 33 AF XY: 0.0589 AC XY: 4386 AN XY: 74462

African (AFR) AF: 0.0294 AC: 1220 AN: 41548

American (AMR) AF: 0.0570 AC: 872 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 425 AN: 3468

East Asian (EAS) AF: 0.0978 AC: 506 AN: 5176

South Asian (SAS) AF: 0.102 AC: 492 AN: 4806

European-Finnish (FIN) AF: 0.0336 AC: 357 AN: 10626

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0745 AC: 5070 AN: 68034

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

Alfa AF: 0.0772 Hom.: 1001

Bravo AF: 0.0616

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.80
DANN	Benign	0.52
PhyloP100		-1.2
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: rs17665859; hg19: chr8-445601;