rs73352472

Variant names:

• chr14-103963069-C-T
• rs73352472
• NM_153046.3:c.323-10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_153046.3(TDRD9):​c.323-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,519,724 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0096 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (21 hom.)
• Consequence: TDRD9 NM_153046.3 intron
• Scores: Splicing: ADA: 0.00008053
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.85
• Publications: 1 publications found

Genes affected

TDRD9 (HGNC:20122): (tudor domain containing 9) Predicted to enable RNA binding activity. Involved in spermatogenesis. Located in cytoplasm and nucleus. Implicated in spermatogenic failure 30. [provided by Alliance of Genome Resources, Apr 2022]

TDRD9 Gene-Disease associations (from GenCC):

• spermatogenic failure 30

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-103963069-C-T is Benign according to our data. Variant chr14-103963069-C-T is described in ClinVar as Benign. ClinVar VariationId is 789823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00964 (1464/151806) while in subpopulation AFR AF = 0.034 (1406/41358). AF 95% confidence interval is 0.0325. There are 23 homozygotes in GnomAd4. There are 672 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153046.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD9	NM_153046.3	MANE Select	c.323-10C>T		intron	N/A	NP_694591.2	Q8NDG6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TDRD9	ENST00000409874.9	TSL:5 MANE Select	c.323-10C>T		intron	N/A	ENSP00000387303.4	Q8NDG6-1
	TDRD9	ENST00000967811.1		c.323-10C>T		intron	N/A	ENSP00000637870.1
	TDRD9	ENST00000967812.1		c.323-10C>T		intron	N/A	ENSP00000637871.1

Frequencies

GnomAD3 genomes AF: 0.00960 AC: 1456 AN: 151692 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00480

GnomAD2 exomes AF: 0.00228 AC: 314 AN: 137864 AF XY: 0.00170

Gnomad AFR exome AF: 0.0364

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000144

Gnomad OTH exome AF: 0.00105

GnomAD4 exome AF: 0.000993 AC: 1359 AN: 1367918 Hom.: 21 Cov.: 26 AF XY: 0.000865 AC XY: 584 AN XY: 675468

African (AFR) AF: 0.0357 AC: 1085 AN: 30360

American (AMR) AF: 0.00189 AC: 58 AN: 30658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24130

East Asian (EAS) AF: 0.00 AC: 0 AN: 35180

South Asian (SAS) AF: 0.000120 AC: 9 AN: 75110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48856

Middle Eastern (MID) AF: 0.00179 AC: 10 AN: 5598

European-Non Finnish (NFE) AF: 0.0000565 AC: 60 AN: 1061308

Other (OTH) AF: 0.00242 AC: 137 AN: 56718

GnomAD4 genome AF: 0.00964 AC: 1464 AN: 151806 Hom.: 23 Cov.: 32 AF XY: 0.00906 AC XY: 672 AN XY: 74164

African (AFR) AF: 0.0340 AC: 1406 AN: 41358

American (AMR) AF: 0.00230 AC: 35 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67970

Other (OTH) AF: 0.00475 AC: 10 AN: 2106

Alfa AF: 0.00732 Hom.: 4

Bravo AF: 0.0109

Asia WGS AF: 0.00375 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.48
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000081
dbscSNV1_RF	Benign	0.0020
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: rs73352472; hg19: chr14-104429406;