rs373283697

Variant names:

• chr4-146867584-C-A
• NM_031956.4:c.800-1G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-146867584-C-A
• chr4-146867584-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_031956.4(TTC29):​c.800-1G>T variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.00000229 in 1,311,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: TTC29 NM_031956.4 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.06022409 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.6, offset of 48, new splice context is: ctcttactacttgggcttAGcac. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC29	NM_031956.4	c.800-1G>T		splice_acceptor_variant, intron_variant	Intron 7 of 12	ENST00000325106.9	NP_114162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC29	ENST00000325106.9	c.800-1G>T		splice_acceptor_variant, intron_variant	Intron 7 of 12	1	NM_031956.4	ENSP00000316740.4
TTC29	ENST00000508306.5	n.800-1G>T		splice_acceptor_variant, intron_variant	Intron 7 of 13	1		ENSP00000422648.1
TTC29	ENST00000513335.5	c.878-1G>T		splice_acceptor_variant, intron_variant	Intron 8 of 13	2		ENSP00000423505.1
TTC29	ENST00000504425.5	c.800-1G>T		splice_acceptor_variant, intron_variant	Intron 7 of 12	5		ENSP00000425778.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1311090 Hom.: 0 Cov.: 21 AF XY: 0.00000308 AC XY: 2 AN XY: 649898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000349

Gnomad4 ASJ exome AF: 0.0000430

Gnomad4 EAS exome AF: 0.0000285

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
GERP RS		5.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.97		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-147788736;