NM_173538.3:c.467T>C

Variant names:

• chr8-87206028-T-C
• rs1404442288
• NM_173538.3:c.467T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173538.3(CNBD1):​c.467T>C​(p.Val156Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CNBD1 NM_173538.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 0 publications found

Genes affected

CNBD1 (HGNC:26663): (cyclic nucleotide binding domain containing 1)

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_173538.3. 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
	CNBD1	NM_173538.3	MANE Select	c.467T>C	p.Val156Ala	missense	Exon 5 of 11	NP_775809.1	Q8NA66

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNBD1	ENST00000518476.6	TSL:1 MANE Select	c.467T>C	p.Val156Ala	missense	Exon 5 of 11	ENSP00000430073.1	Q8NA66
	CNBD1	ENST00000523299.6	TSL:3	c.467T>C	p.Val156Ala	missense	Exon 5 of 13	ENSP00000430986.2	H0YC59
	CNBD1	ENST00000522427.1	TSL:4	n.210T>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444210 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717582

African (AFR) AF: 0.00 AC: 0 AN: 32650

American (AMR) AF: 0.00 AC: 0 AN: 42026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25642

East Asian (EAS) AF: 0.00 AC: 0 AN: 38796

South Asian (SAS) AF: 0.00 AC: 0 AN: 83740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103594

Other (OTH) AF: 0.00 AC: 0 AN: 59716

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.37	T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	0.90	L
PhyloP100		3.6
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.37		Gain of catalytic residue at V156 (P = 0.0099)
MVP		0.38
MPC		0.012
ClinPred		0.95	D
GERP RS		5.3
PromoterAI		0.023	Neutral
Varity_R		0.18
gMVP		0.22
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1404442288; hg19: chr8-88218256;