17-42807801-G-A

Position:

• chr17-42807801-G-A

Variant summary

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

The NM_173478.3(CNTD1):​c.759G>A​(p.Met253Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTD1 NM_173478.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.84

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTD1	NM_173478.3	c.759G>A	p.Met253Ile	missense_variant	6/7	ENST00000588408.6
CNTD1	NM_001330222.2	c.510G>A	p.Met170Ile	missense_variant	6/7
CNTD1	XM_024450569.2	c.603G>A	p.Met201Ile	missense_variant	6/7
CNTD1	XM_011524311.3	c.510G>A	p.Met170Ile	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTD1	ENST00000588408.6	c.759G>A	p.Met253Ile	missense_variant	6/7	1	NM_173478.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jan 31, 2023

The c.759G>A (p.M253I) alteration is located in exon 6 (coding exon 6) of the CNTD1 gene. This alteration results from a G to A substitution at nucleotide position 759, causing the methionine (M) at amino acid position 253 to be replaced by an isoleucine (I). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T;.
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.64	T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.64
MutPred		0.50		Gain of methylation at K249 (P = 0.0666);.;.;
MVP		0.82
MPC		0.79
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.71
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: -33

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: chr17-40959819;