TTLL9 p.Asp197Asp

Variant names:

• chr20-31922977-T-T
• NM_001008409.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr20-31922978--
• chr20-31922980-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001008409.5(TTLL9):​c. variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTLL9 NM_001008409.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.28
• Publications: 0 publications found

Genes affected

TTLL9 (HGNC:16118): (tubulin tyrosine ligase like 9) Predicted to enable tubulin binding activity and tubulin-glutamic acid ligase activity. Predicted to be involved in microtubule cytoskeleton organization and protein polyglutamylation. Predicted to act upstream of or within flagellated sperm motility. Predicted to be located in ciliary basal body; cytoplasm; and microtubule. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

TTLL9 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008409.5. 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
	TTLL9	NM_001008409.5	MANE Select	c.		intron	N/A	NP_001008409.1	Q3SXZ7-1
	TTLL9	NM_001367620.2		c.		intron	N/A	NP_001354549.1	A0A087X135
	TTLL9	NR_134519.4		n.		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL9	ENST00000535842.6	TSL:5 MANE Select	c.		splice_donor intron	N/A	ENSP00000442515.1	Q3SXZ7-1
	TTLL9	ENST00000620043.4	TSL:1	c.		splice_donor intron	N/A	ENSP00000483865.1	A0A087X135
	TTLL9	ENST00000310998.8	TSL:1	n.		splice_donor intron	N/A	ENSP00000308980.5	A0A0A0MR21

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-30510780;