3-133574093-G-A

Position:

• chr3-133574093-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017548.5(CDV3):​c.49G>A​(p.Asp17Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDV3 NM_017548.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

CDV3 (HGNC:26928): (CDV3 homolog) Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30045122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDV3	NM_017548.5	c.49G>A	p.Asp17Asn	missense_variant	1/5	ENST00000264993.8	NP_060018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDV3	ENST00000264993.8	c.49G>A	p.Asp17Asn	missense_variant	1/5	1	NM_017548.5	ENSP00000264993.3
CDV3	ENST00000431519.6	c.49G>A	p.Asp17Asn	missense_variant	1/5	1		ENSP00000391955.2
CDV3	ENST00000688838.1	c.49G>A	p.Asp17Asn	missense_variant	1/5			ENSP00000508628.1
CDV3	ENST00000503932.6	n.49G>A		non_coding_transcript_exon_variant	1/5	4		ENSP00000421340.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1092284 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 538616

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Feb 07, 2023

The c.49G>A (p.D17N) alteration is located in exon 1 (coding exon 1) of the CDV3 gene. This alteration results from a G to A substitution at nucleotide position 49, causing the aspartic acid (D) at amino acid position 17 to be replaced by an asparagine (N). 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	1.0
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;.
Eigen	Benign	-0.033
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.83	T;T
M_CAP	Pathogenic	0.72	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.081
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.040	D;D
Polyphen		0.15	B;B
Vest4		0.34
MutPred		0.30		Loss of glycosylation at K21 (P = 0.0433);Loss of glycosylation at K21 (P = 0.0433);
MVP		0.45
MPC		1.3
ClinPred		0.99	D
GERP RS		1.8
Varity_R		0.55
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-133292937;