rs2084414

Positions:

• chr8-541735-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384899.1(TDRP):​c.108+2915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,050 control chromosomes in the GnomAD database, including 42,990 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 0.75 (42990 hom., cov: 32)
• Consequence: TDRP NM_001384899.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270

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 (AMR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TDRP	NM_001384899.1	c.108+2915C>T		intron_variant		ENST00000324079.11	NP_001371828.1
TDRP	XM_047421392.1	c.-26523C>T		5_prime_UTR_variant	2/4		XP_047277348.1
TDRP	NM_001256113.2	c.108+2915C>T		intron_variant			NP_001243042.1
TDRP	NM_175075.5	c.108+2915C>T		intron_variant			NP_778250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TDRP	ENST00000324079.11	c.108+2915C>T		intron_variant		1	NM_001384899.1	ENSP00000315111	P1
TDRP	ENST00000523656.5	c.108+2915C>T		intron_variant		5		ENSP00000430325

Frequencies

GnomAD3 genomes AF: 0.750 AC: 113905 AN: 151932 Hom.: 42933 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.750 AC: 114024 AN: 152050 Hom.: 42990 Cov.: 32 AF XY: 0.742 AC XY: 55138 AN XY: 74326

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.765

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.773

Alfa AF: 0.768 Hom.: 92675

Bravo AF: 0.765

Asia WGS AF: 0.777 AC: 2704 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	0.79
DANN	Benign	0.39

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: rs2084414; hg19: chr8-491735;