4-146803791-C-T

Variant names:

• chr4-146803791-C-T
• rs7694666
• NM_031956.4:c.1102-106G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031956.4(TTC29):​c.1102-106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 652,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: TTC29 NM_031956.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.1102-106G>A		intron	N/A	NP_114162.2	Q8NA56-1
	TTC29	NM_001300761.4		c.1180-106G>A		intron	N/A	NP_001287690.1	G5E9Z5
	TTC29	NM_001317806.3		c.1102-106G>A		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.1102-106G>A		intron	N/A	ENSP00000316740.4	Q8NA56-1
	TTC29	ENST00000508306.5	TSL:1	n.*164-106G>A		intron	N/A	ENSP00000422648.1	E7EQZ6
	TTC29	ENST00000513335.5	TSL:2	c.1180-106G>A		intron	N/A	ENSP00000423505.1	G5E9Z5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000766 AC: 5 AN: 652322 Hom.: 0 AF XY: 0.00000908 AC XY: 3 AN XY: 330494

African (AFR) AF: 0.00 AC: 0 AN: 16416

American (AMR) AF: 0.00 AC: 0 AN: 18166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14538

East Asian (EAS) AF: 0.00 AC: 0 AN: 31530

South Asian (SAS) AF: 0.00 AC: 0 AN: 42964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2322

European-Non Finnish (NFE) AF: 0.0000108 AC: 5 AN: 464838

Other (OTH) AF: 0.00 AC: 0 AN: 32228

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0030
DANN	Benign	0.62
PhyloP100		-2.0

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: rs7694666; hg19: chr4-147724943;