4-146706824-C-T

Variant names:

• chr4-146706824-C-T
• rs1579486914
• NM_031956.4:c.*334G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_031956.4(TTC29):​c.*334G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC29 NM_031956.4 3_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: -0.124
• Publications: 0 publications found

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]

TTC29 Gene-Disease associations (from GenCC):

• spermatogenic failure 42

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 4-146706824-C-T is Pathogenic according to our data. Variant chr4-146706824-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 805956.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86). . Strength limited to SUPPORTING due to the PP5.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031956.4. 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
	TTC29	NM_031956.4	MANE Select	c.*334G>A		3_prime_UTR	Exon 13 of 13	NP_114162.2	Q8NA56-1
	TTC29	NM_001300761.4		c.*334G>A		3_prime_UTR	Exon 14 of 14	NP_001287690.1	G5E9Z5
	TTC29	NM_001317806.3		c.*334G>A		3_prime_UTR	Exon 13 of 13	NP_001304735.1	E7EQ14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC29	ENST00000325106.9	TSL:1 MANE Select	c.*334G>A		3_prime_UTR	Exon 13 of 13	ENSP00000316740.4	Q8NA56-1
	TTC29	ENST00000513335.5	TSL:2	c.*334G>A		3_prime_UTR	Exon 14 of 14	ENSP00000423505.1	G5E9Z5
	TTC29	ENST00000508306.5	TSL:1	n.*824G>A		downstream_gene	N/A	ENSP00000422648.1	E7EQZ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30486 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 15610

African (AFR) AF: 0.00 AC: 0 AN: 1364

American (AMR) AF: 0.00 AC: 0 AN: 1008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1254

East Asian (EAS) AF: 0.00 AC: 0 AN: 2190

South Asian (SAS) AF: 0.00 AC: 0 AN: 420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 20742

Other (OTH) AF: 0.00 AC: 0 AN: 2282

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Spermatogenic failure 42 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		-0.12
Mutation Taster		=45/55	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs1579486914; hg19: chr4-147627976;