17-42799137-A-G

Variant summary

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

The NM_173478.3(CNTD1):c.70A>G(p.Thr24Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CNTD1 NM_173478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

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=0.09709823).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTD1	NM_173478.3	c.70A>G	p.Thr24Ala	missense_variant	1/7	ENST00000588408.6
CNTD1	NM_001330222.2	c.-81+119A>G		intron_variant
CNTD1	XM_011524311.3	c.-5+307A>G		intron_variant
CNTD1	XM_024450569.2	c.13+307A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTD1	ENST00000588408.6	c.70A>G	p.Thr24Ala	missense_variant	1/7	1	NM_173478.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2022

The c.70A>G (p.T24A) alteration is located in exon 1 (coding exon 1) of the CNTD1 gene. This alteration results from a A to G substitution at nucleotide position 70, causing the threonine (T) at amino acid position 24 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.74	D;D
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.22	T
Polyphen		0.043	B
Vest4		0.35
MutPred		0.21		Loss of catalytic residue at T24 (P = 0.0441);
MVP		0.32
MPC		0.23
ClinPred		0.69	D
GERP RS		5.0
Varity_R		0.12
gMVP		0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs2054727014; hg19: chr17-40951155;