rs17665859

Positions:

• chr8-495601-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1	c.109-1004A>G		intron_variant		ENST00000324079.11	NP_001371828.1
TDRP	NM_001256113.2	c.109-1004A>G		intron_variant			NP_001243042.1
TDRP	NM_175075.5	c.109-1004A>G		intron_variant			NP_778250.2
TDRP	XM_047421392.1	c.139-1004A>G		intron_variant			XP_047277348.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11	c.109-1004A>G		intron_variant		1	NM_001384899.1	ENSP00000315111	P1
TDRP	ENST00000523656.5	c.109-1004A>G		intron_variant		5		ENSP00000430325

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

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0978

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0745

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0786 Hom.: 781

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

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: rs17665859; hg19: chr8-445601;