4-146923272-A-G

Variant names:

• chr4-146923272-A-G
• rs1995809
• NM_031956.4:c.177-14023T>C

Variant summary

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

The NM_031956.4(TTC29):​c.177-14023T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,692 control chromosomes in the GnomAD database, including 3,028 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 0.16 (3028 hom., cov: 32)
• Consequence: TTC29 NM_031956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC29	NM_031956.4	c.177-14023T>C		intron_variant	Intron 4 of 12	ENST00000325106.9	NP_114162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC29	ENST00000325106.9	c.177-14023T>C		intron_variant	Intron 4 of 12	1	NM_031956.4	ENSP00000316740.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23870 AN: 151574 Hom.: 3001 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0874

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.158 AC: 23953 AN: 151692 Hom.: 3028 Cov.: 32 AF XY: 0.160 AC XY: 11873 AN XY: 74146

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.141

Alfa AF: 0.118 Hom.: 206

Bravo AF: 0.174

Asia WGS AF: 0.186 AC: 646 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.22

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: rs1995809; hg19: chr4-147844424;