3-149210281-G-T

Position:

• chr3-149210281-G-T

Variant summary

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

The NM_000096.4(CP):​c.493C>A​(p.Gln165Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CP NM_000096.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14

Genes affected

CP (HGNC:2295): (ceruloplasmin) The protein encoded by this gene is a metalloprotein that binds most of the copper in plasma and is involved in the peroxidation of Fe(II)transferrin to Fe(III) transferrin. Mutations in this gene cause aceruloplasminemia, which results in iron accumulation and tissue damage, and is associated with diabetes and neurologic abnormalities. Two transcript variants, one protein-coding and the other not protein-coding, have been found for this gene. [provided by RefSeq, Feb 2012]

CP (HGNC:):

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	Protein	UniProt
CP	NM_000096.4	c.493C>A	p.Gln165Lys	missense_variant	3/19	ENST00000264613.11	NP_000087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CP	ENST00000264613.11	c.493C>A	p.Gln165Lys	missense_variant	3/19	1	NM_000096.4	ENSP00000264613.6
CP	ENST00000490639.5	n.525C>A		non_coding_transcript_exon_variant	3/17	1
CP	ENST00000481169.5	n.493C>A		non_coding_transcript_exon_variant	3/18	2		ENSP00000418773.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727198

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: 0.00000809

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	20
DANN	Uncertain	0.99
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Pathogenic	0.86	D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.47
Sift	Benign	0.25	T
Sift4G	Benign	0.099	T
Vest4		0.45
MutPred		0.43		Gain of ubiquitination at Q165 (P = 0.0104);
MVP		0.95
MPC		0.37
ClinPred		0.98	D
GERP RS		5.8
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs386134122; hg19: chr3-148928068;