20-31922980-C-T

Variant names:

• chr20-31922980-C-T
• rs749750682
• NM_001008409.5:c.591C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001008409.5(TTLL9):​c.591C>T​(p.Asp197Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000502 in 1,613,594 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: TTLL9 NM_001008409.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-1.34 with no splicing effect.

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.591C>T	p.Asp197Asp	synonymous	Exon 8 of 15	NP_001008409.1	Q3SXZ7-1
	TTLL9	NM_001367620.2		c.252C>T	p.Asp84Asp	synonymous	Exon 5 of 12	NP_001354549.1	A0A087X135
	TTLL9	NR_134519.4		n.998C>T		non_coding_transcript_exon	Exon 9 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTLL9	ENST00000535842.6	TSL:5 MANE Select	c.591C>T	p.Asp197Asp	synonymous	Exon 8 of 15	ENSP00000442515.1	Q3SXZ7-1
	TTLL9	ENST00000620043.4	TSL:1	c.252C>T	p.Asp84Asp	synonymous	Exon 5 of 12	ENSP00000483865.1	A0A087X135
	TTLL9	ENST00000310998.8	TSL:1	n.*286C>T		non_coding_transcript_exon	Exon 8 of 15	ENSP00000308980.5	A0A0A0MR21

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249506 AF XY: 0.0000443

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000520 AC: 76 AN: 1461392 Hom.: 0 Cov.: 30 AF XY: 0.0000564 AC XY: 41 AN XY: 727036

African (AFR) AF: 0.0000896 AC: 3 AN: 33466

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000576 AC: 64 AN: 1111648

Other (OTH) AF: 0.0000331 AC: 2 AN: 60362

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_noAF	Benign	-0.46
CADD	Benign	1.8
DANN	Benign	0.57
PhyloP100		-1.3

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: rs749750682; hg19: chr20-30510783; COSMIC: COSV60595785;