rs7694666

Positions:

• chr4-146803791-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031956.4(TTC29):​c.1102-106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 804,420 control chromosomes in the GnomAD database, including 1,018 homozygotes. 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 0.046 (231 hom., cov: 32)
  • Exomes 𝑓: 0.038 (787 hom.)
• Consequence: TTC29 NM_031956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC29	NM_031956.4	c.1102-106G>C		intron_variant		ENST00000325106.9	NP_114162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC29	ENST00000325106.9	c.1102-106G>C		intron_variant		1	NM_031956.4	ENSP00000316740	P4

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6989 AN: 152176 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0376 AC: 24490 AN: 652126 Hom.: 787 AF XY: 0.0392 AC XY: 12942 AN XY: 330394

Gnomad4 AFR exome AF: 0.0743

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0194

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.0867

Gnomad4 FIN exome AF: 0.0297

Gnomad4 NFE exome AF: 0.0259

Gnomad4 OTH exome AF: 0.0359

GnomAD4 genome AF: 0.0459 AC: 6995 AN: 152294 Hom.: 231 Cov.: 32 AF XY: 0.0468 AC XY: 3487 AN XY: 74468

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.0299

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.0923

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0385 Hom.: 15

Bravo AF: 0.0485

Asia WGS AF: 0.0910 AC: 318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs7694666; hg19: chr4-147724943;