NM_001365709.1:c.415C>G

Variant names:

• chr20-35983989-C-G
• rs200885142
• NM_001365709.1:c.415C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365709.1(CNBD2):​c.415C>G​(p.Arg139Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R139H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CNBD2 NM_001365709.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• Publications: 5 publications found

Genes affected

CNBD2 (HGNC:16145): (cyclic nucleotide binding domain containing 2) Predicted to enable cAMP binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365709.1. 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
	CNBD2	NM_001365709.1	MANE Select	c.415C>G	p.Arg139Gly	missense	Exon 5 of 12	NP_001352638.1	Q96M20-1
	CNBD2	NM_080834.4		c.415C>G	p.Arg139Gly	missense	Exon 5 of 12	NP_543024.2	Q96M20-2
	CNBD2	NM_001207076.3		c.415C>G	p.Arg139Gly	missense	Exon 5 of 11	NP_001194005.1	Q96M20-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD2	ENST00000373973.7	TSL:5 MANE Select	c.415C>G	p.Arg139Gly	missense	Exon 5 of 12	ENSP00000363084.3	Q96M20-1
	CNBD2	ENST00000538900.1	TSL:1	c.415C>G	p.Arg139Gly	missense	Exon 5 of 11	ENSP00000442729.1	Q96M20-3
	CNBD2	ENST00000463258.6	TSL:1	n.408-638C>G		intron	N/A	ENSP00000476014.1	U3KQM1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.082	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Pathogenic	2.9	M
PhyloP100		3.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.54
Sift	Benign	0.16	T
Sift4G	Uncertain	0.017	D
Polyphen		0.34	B
Vest4		0.65
MutPred		0.54		Loss of solvent accessibility (P = 0.0159)
MVP		0.80
MPC		0.38
ClinPred		0.88	D
GERP RS		5.5
Varity_R		0.41
gMVP		0.49
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs200885142; hg19: chr20-34571911;