NM_031956.4:c.885+905A>G

Variant names:

• chr4-146866593-T-C
• rs1396716
• NM_031956.4:c.885+905A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031956.4(TTC29):​c.885+905A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 151,946 control chromosomes in the GnomAD database, including 35,918 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 0.67 (35918 hom., cov: 31)
• Consequence: TTC29 NM_031956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 3 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 = 0.909 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC29	NM_031956.4	MANE Select	c.885+905A>G		intron	N/A	NP_114162.2
	TTC29	NM_001300761.4		c.963+905A>G		intron	N/A	NP_001287690.1
	TTC29	NM_001317806.3		c.885+905A>G		intron	N/A	NP_001304735.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC29	ENST00000325106.9	TSL:1 MANE Select	c.885+905A>G		intron	N/A	ENSP00000316740.4
	TTC29	ENST00000508306.5	TSL:1	n.885+905A>G		intron	N/A	ENSP00000422648.1
	TTC29	ENST00000513335.5	TSL:2	c.963+905A>G		intron	N/A	ENSP00000423505.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101012 AN: 151828 Hom.: 35854 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.666 AC: 101129 AN: 151946 Hom.: 35918 Cov.: 31 AF XY: 0.670 AC XY: 49752 AN XY: 74272

African (AFR) AF: 0.917 AC: 38057 AN: 41496

American (AMR) AF: 0.687 AC: 10467 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2064 AN: 3466

East Asian (EAS) AF: 0.754 AC: 3879 AN: 5146

South Asian (SAS) AF: 0.664 AC: 3193 AN: 4812

European-Finnish (FIN) AF: 0.592 AC: 6248 AN: 10558

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35143 AN: 67926

Other (OTH) AF: 0.647 AC: 1363 AN: 2106

Alfa AF: 0.543 Hom.: 33373

Bravo AF: 0.683

Asia WGS AF: 0.753 AC: 2618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.032
DANN	Benign	0.45
PhyloP100		-1.9
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: rs1396716; hg19: chr4-147787745;