17-42805722-A-T

Variant names:

• chr17-42805722-A-T
• rs764472001
• NM_173478.3:c.418A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173478.3(CNTD1):​c.418A>T​(p.Ile140Leu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTD1 NM_173478.3 missense, splice_region
• Scores: Splicing: ADA: 0.005632
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.64

Genes affected

CNTD1 (HGNC:26847): (cyclin N-terminal domain containing 1) Predicted to be involved in reciprocal meiotic recombination. Predicted to act upstream of or within spermatogenesis. Predicted to be active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25306654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTD1	NM_173478.3	c.418A>T	p.Ile140Leu	missense_variant, splice_region_variant	Exon 4 of 7	ENST00000588408.6	NP_775749.2
CNTD1	NM_001330222.2	c.169A>T	p.Ile57Leu	missense_variant, splice_region_variant	Exon 4 of 7		NP_001317151.1
CNTD1	XM_024450569.2	c.262A>T	p.Ile88Leu	missense_variant, splice_region_variant	Exon 4 of 7		XP_024306337.1
CNTD1	XM_011524311.3	c.169A>T	p.Ile57Leu	missense_variant, splice_region_variant	Exon 3 of 6		XP_011522613.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTD1	ENST00000588408.6	c.418A>T	p.Ile140Leu	missense_variant, splice_region_variant	Exon 4 of 7	1	NM_173478.3	ENSP00000465204.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0069	T;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.45	P;.;.
Vest4		0.25
MutPred		0.24		Loss of sheet (P = 0.0457);.;.;
MVP		0.52
MPC		0.54
ClinPred		0.86	D
GERP RS		4.6
Varity_R		0.42
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0056
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs764472001; hg19: chr17-40957740;