rs7694666

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-146803791-C-G
• chr4-146803791-C-T

Variant summary

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

The NM_031956.4(TTC29):​c.1102-106G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0391 in 804,420 control chromosomes in the GnomAD database, including 1,018 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 0.046 (231 hom., cov: 32)
  • Exomes 𝑓: 0.038 (787 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 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.1102-106G>C		intron	N/A	NP_114162.2
	TTC29	NM_001300761.4		c.1180-106G>C		intron	N/A	NP_001287690.1
	TTC29	NM_001317806.3		c.1102-106G>C		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.1102-106G>C		intron	N/A	ENSP00000316740.4
	TTC29	ENST00000508306.5	TSL:1	n.*164-106G>C		intron	N/A	ENSP00000422648.1
	TTC29	ENST00000513335.5	TSL:2	c.1180-106G>C		intron	N/A	ENSP00000423505.1

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6989 AN: 152176 Hom.: 232 Cov.: 32

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0376 AC: 24490 AN: 652126 Hom.: 787 AF XY: 0.0392 AC XY: 12942 AN XY: 330394

African (AFR) AF: 0.0743 AC: 1218 AN: 16402

American (AMR) AF: 0.0340 AC: 618 AN: 18158

Ashkenazi Jewish (ASJ) AF: 0.0194 AC: 282 AN: 14538

East Asian (EAS) AF: 0.142 AC: 4484 AN: 31526

South Asian (SAS) AF: 0.0867 AC: 3723 AN: 42934

European-Finnish (FIN) AF: 0.0297 AC: 872 AN: 29316

Middle Eastern (MID) AF: 0.0495 AC: 115 AN: 2322

European-Non Finnish (NFE) AF: 0.0259 AC: 12021 AN: 464716

Other (OTH) AF: 0.0359 AC: 1157 AN: 32214

GnomAD4 genome AF: 0.0459 AC: 6995 AN: 152294 Hom.: 231 Cov.: 32 AF XY: 0.0468 AC XY: 3487 AN XY: 74468

African (AFR) AF: 0.0741 AC: 3080 AN: 41566

American (AMR) AF: 0.0299 AC: 457 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.136 AC: 704 AN: 5174

South Asian (SAS) AF: 0.0923 AC: 446 AN: 4832

European-Finnish (FIN) AF: 0.0246 AC: 261 AN: 10616

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1868 AN: 68024

Other (OTH) AF: 0.0407 AC: 86 AN: 2112

Alfa AF: 0.0385 Hom.: 15

Bravo AF: 0.0485

Asia WGS AF: 0.0910 AC: 318 AN: 3478

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	0.66
PhyloP100		-2.0
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: rs7694666; hg19: chr4-147724943;