NM_031956.4:c.940G>T

Variant names:

• chr4-146833843-C-A
• NM_031956.4:c.940G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031956.4(TTC29):​c.940G>T​(p.Gly314Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: TTC29 NM_031956.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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]

LOC105377474 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC29	NM_031956.4	c.940G>T	p.Gly314Trp	missense_variant	Exon 9 of 13	ENST00000325106.9	NP_114162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC29	ENST00000325106.9	c.940G>T	p.Gly314Trp	missense_variant	Exon 9 of 13	1	NM_031956.4	ENSP00000316740.4
TTC29	ENST00000508306.5	n.940G>T		non_coding_transcript_exon_variant	Exon 9 of 14	1		ENSP00000422648.1
TTC29	ENST00000513335.5	c.1018G>T	p.Gly340Trp	missense_variant	Exon 10 of 14	2		ENSP00000423505.1
TTC29	ENST00000504425.5	c.940G>T	p.Gly314Trp	missense_variant	Exon 9 of 13	5		ENSP00000425778.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461038 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726800

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

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
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.82	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.9	.;M;.
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Pathogenic	0.65
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.011	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.81
MutPred		0.59		Loss of disorder (P = 0.0193);.;.;
MVP		0.67
MPC		0.12
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.76
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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: chr4-147754995;