4-146903704-GTTATTATGTACATC-G

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_031956.4(TTC29):c.412_425del(p.Asp138LeufsTer10) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TTC29 NM_031956.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.42

Genes affected

TTC29 (HGNC:29936): (tetratricopeptide repeat domain 29) Involved in cilium movement and cilium organization. Located in sperm flagellum. Implicated in spermatogenic failure 42. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-146903704-GTTATTATGTACATC-G is Pathogenic according to our data. Variant chr4-146903704-GTTATTATGTACATC-G is described in ClinVar as [Pathogenic]. Clinvar id is 805960.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr4-146903704-GTTATTATGTACATC-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC29	NM_031956.4	c.412_425del	p.Asp138LeufsTer10	frameshift_variant	6/13	ENST00000325106.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC29	ENST00000325106.9	c.412_425del	p.Asp138LeufsTer10	frameshift_variant	6/13	1	NM_031956.4	P4
TTC29	ENST00000508306.5	c.412_425del	p.Asp138LeufsTer10	frameshift_variant, NMD_transcript_variant	6/14	1
TTC29	ENST00000504425.5	c.412_425del	p.Asp138LeufsTer10	frameshift_variant	6/13	5		A1
TTC29	ENST00000513335.5	c.490_503del	p.Asp164LeufsTer10	frameshift_variant	7/14	2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 42 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 23, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1579951018; hg19: chr4-147824856;