4-146923272-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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: Benign. The variant received -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.

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.177-14023T>C		intron	N/A	NP_114162.2	Q8NA56-1
	TTC29	NM_001300761.4		c.255-14023T>C		intron	N/A	NP_001287690.1	G5E9Z5
	TTC29	NM_001317806.3		c.177-14023T>C		intron	N/A	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.177-14023T>C		intron	N/A	ENSP00000316740.4	Q8NA56-1
	TTC29	ENST00000508306.5	TSL:1	n.177-14023T>C		intron	N/A	ENSP00000422648.1	E7EQZ6
	TTC29	ENST00000513335.5	TSL:2	c.255-14023T>C		intron	N/A	ENSP00000423505.1	G5E9Z5

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

African (AFR) AF: 0.339 AC: 14045 AN: 41418

American (AMR) AF: 0.171 AC: 2591 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 428 AN: 3464

East Asian (EAS) AF: 0.187 AC: 968 AN: 5178

South Asian (SAS) AF: 0.129 AC: 621 AN: 4810

European-Finnish (FIN) AF: 0.0874 AC: 925 AN: 10580

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0590 AC: 3998 AN: 67762

Other (OTH) AF: 0.141 AC: 295 AN: 2098

Alfa AF: 0.125 Hom.: 536

Bravo AF: 0.174

Asia WGS AF: 0.186 AC: 646 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.22
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1995809; hg19: chr4-147844424;