chr14-103965443-C-T

Variant names:

• chr14-103965443-C-T
• rs201249896
• NM_153046.3:c.531C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_153046.3(TDRD9):​c.531C>T​(p.Ser177Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000199 in 1,551,538 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: TDRD9 NM_153046.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.87
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 14-103965443-C-T is Benign according to our data. Variant chr14-103965443-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3049271.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.87 with no splicing effect.

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.531C>T	p.Ser177Ser	synonymous	Exon 4 of 36	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.531C>T	p.Ser177Ser	synonymous	Exon 4 of 36	ENSP00000387303.4	Q8NDG6-1
	TDRD9	ENST00000967811.1		c.531C>T	p.Ser177Ser	synonymous	Exon 4 of 35	ENSP00000637870.1
	TDRD9	ENST00000967812.1		c.531C>T	p.Ser177Ser	synonymous	Exon 4 of 35	ENSP00000637871.1

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152012 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000428 AC: 67 AN: 156584 AF XY: 0.000482

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00612

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000198

Gnomad OTH exome AF: 0.000455

GnomAD4 exome AF: 0.000192 AC: 268 AN: 1399406 Hom.: 1 Cov.: 32 AF XY: 0.000217 AC XY: 150 AN XY: 690210

African (AFR) AF: 0.000127 AC: 4 AN: 31598

American (AMR) AF: 0.0000280 AC: 1 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00691 AC: 174 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000491 AC: 53 AN: 1078974

Other (OTH) AF: 0.000586 AC: 34 AN: 58000

GnomAD4 genome AF: 0.000270 AC: 41 AN: 152132 Hom.: 1 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74368

African (AFR) AF: 0.000120 AC: 5 AN: 41502

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00836 AC: 29 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000461 Hom.: 0

Bravo AF: 0.000268

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TDRD9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.37
DANN	Benign	0.69
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

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: rs201249896; hg19: chr14-104431780;