rs985103553

Variant names:

• chr4-146803681-T-C
• rs985103553
• NM_031956.4:c.1106A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-146803681-T-C
• chr4-146803681-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031956.4(TTC29):​c.1106A>G​(p.Tyr369Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. Y369S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TTC29 NM_031956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15456587).

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.1106A>G	p.Tyr369Cys	missense	Exon 11 of 13	NP_114162.2	Q8NA56-1
	TTC29	NM_001300761.4		c.1184A>G	p.Tyr395Cys	missense	Exon 12 of 14	NP_001287690.1	G5E9Z5
	TTC29	NM_001317806.3		c.1106A>G	p.Tyr369Cys	missense	Exon 11 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.1106A>G	p.Tyr369Cys	missense	Exon 11 of 13	ENSP00000316740.4	Q8NA56-1
	TTC29	ENST00000508306.5	TSL:1	n.*168A>G		non_coding_transcript_exon	Exon 12 of 14	ENSP00000422648.1	E7EQZ6
	TTC29	ENST00000508306.5	TSL:1	n.*168A>G		3_prime_UTR	Exon 12 of 14	ENSP00000422648.1	E7EQZ6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424222 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 703368

⚠️ 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: 32764

American (AMR) AF: 0.00 AC: 0 AN: 41198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 39020

South Asian (SAS) AF: 0.00 AC: 0 AN: 82048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4934

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1088872

Other (OTH) AF: 0.00 AC: 0 AN: 58678

⚠️ 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

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.095	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.31
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.31
Sift	Benign	0.16	T
Sift4G	Benign	0.17	T
Polyphen		0.68	P
Vest4		0.19
MVP		0.58
MPC		0.016
ClinPred		0.50	T
GERP RS		1.2
Varity_R		0.085
gMVP		0.11
Mutation Taster		=87/13	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: rs985103553; hg19: chr4-147724833;