rs369571582

Variant names:

• chr4-146867532-T-A
• rs369571582
• NM_031956.4:c.851A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-146867532-T-A
• chr4-146867532-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031956.4(TTC29):​c.851A>T​(p.His284Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,402,400 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H284R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TTC29 NM_031956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.851A>T	p.His284Leu	missense	Exon 8 of 13	NP_114162.2	Q8NA56-1
	TTC29	NM_001300761.4		c.929A>T	p.His310Leu	missense	Exon 9 of 14	NP_001287690.1	G5E9Z5
	TTC29	NM_001317806.3		c.851A>T	p.His284Leu	missense	Exon 8 of 13	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.851A>T	p.His284Leu	missense	Exon 8 of 13	ENSP00000316740.4	Q8NA56-1
	TTC29	ENST00000508306.5	TSL:1	n.851A>T		non_coding_transcript_exon	Exon 8 of 14	ENSP00000422648.1	E7EQZ6
	TTC29	ENST00000513335.5	TSL:2	c.929A>T	p.His310Leu	missense	Exon 9 of 14	ENSP00000423505.1	G5E9Z5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1402400 Hom.: 0 Cov.: 27 AF XY: 0.00000144 AC XY: 1 AN XY: 694488

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31716

American (AMR) AF: 0.00 AC: 0 AN: 38252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24784

East Asian (EAS) AF: 0.00 AC: 0 AN: 37300

South Asian (SAS) AF: 0.0000132 AC: 1 AN: 75674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080828

Other (OTH) AF: 0.00 AC: 0 AN: 57588

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.0063
Eigen_PC	Benign	0.046
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.7
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.35
Sift	Benign	0.046	D
Sift4G	Uncertain	0.013	D
Polyphen		0.62	P
Vest4		0.39
MutPred		0.58		Loss of helix (P = 0.0444)
MVP		0.72
MPC		0.016
ClinPred		0.73	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.44
Mutation Taster		=68/32	polymorphism

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: rs369571582; hg19: chr4-147788684;