chr17-42807801-G-A

Variant names:

• chr17-42807801-G-A
• NM_173478.3:c.759G>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173478.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTD1	NM_173478.3	MANE Select	c.759G>A	p.Met253Ile	missense	Exon 6 of 7	NP_775749.2	Q8N815-1
	CNTD1	NM_001330222.2		c.510G>A	p.Met170Ile	missense	Exon 6 of 7	NP_001317151.1	B4DXR6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTD1	ENST00000588408.6	TSL:1 MANE Select	c.759G>A	p.Met253Ile	missense	Exon 6 of 7	ENSP00000465204.1	Q8N815-1
	CNTD1	ENST00000315066.5	TSL:1	n.371G>A		non_coding_transcript_exon	Exon 4 of 5
	CNTD1	ENST00000588527.5	TSL:2	c.510G>A	p.Met170Ile	missense	Exon 6 of 7	ENSP00000468725.1	B4DXR6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		8.8
PrimateAI	Uncertain	0.64	T
Sift4G	Pathogenic	0.0	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

Other links and lift over

hg19: chr17-40959819;