rs952639

Positions:

• chr4-146780467-G-A
• chr4-146780467-G-C

Variant summary

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

The NM_031956.4(TTC29):​c.1330+22990C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,646 control chromosomes in the GnomAD database, including 4,196 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 0.23 (4196 hom., cov: 31)
• Consequence: TTC29 NM_031956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.937

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC29	NM_031956.4	c.1330+22990C>T		intron_variant		ENST00000325106.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC29	ENST00000325106.9	c.1330+22990C>T		intron_variant		1	NM_031956.4	P4
TTC29	ENST00000508306.5	c.*392+22990C>T		intron_variant, NMD_transcript_variant		1
TTC29	ENST00000504425.5	c.1330+22990C>T		intron_variant		5		A1
TTC29	ENST00000513335.5	c.1408+22990C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34265 AN: 151528 Hom.: 4187 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.226 AC: 34293 AN: 151646 Hom.: 4196 Cov.: 31 AF XY: 0.231 AC XY: 17101 AN XY: 74092

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.234

Alfa AF: 0.247 Hom.: 9861

Bravo AF: 0.222

Asia WGS AF: 0.309 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.43

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: rs952639; hg19: chr4-147701619;