19-48043906-C-T

Variant names:

• chr19-48043906-C-T
• rs1600130570
• NM_019855.5:c.17G>A

Variant summary

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

The NM_019855.5(CABP5):​c.17G>A​(p.Gly6Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000222 in 1,350,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G6V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CABP5 NM_019855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• Publications: 0 publications found

Genes affected

CABP5 (HGNC:13714): (calcium binding protein 5) The product of this gene belongs to a subfamily of calcium binding proteins, which share similarity to calmodulin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Expression of this gene is retina-specific. The mouse homolog of this protein has been shown to express in the inner nuclear layer of the retina, suggested its role in neuronal functioning. The specific function of this gene is unknown. [provided by RefSeq, Oct 2009]

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_019855.5. 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
	CABP5	NM_019855.5	MANE Select	c.17G>A	p.Gly6Asp	missense	Exon 1 of 6	NP_062829.1	Q9NP86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP5	ENST00000293255.3	TSL:1 MANE Select	c.17G>A	p.Gly6Asp	missense	Exon 1 of 6	ENSP00000293255.1	Q9NP86
	CABP5	ENST00000602032.1	TSL:3	n.-25G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1350810 Hom.: 0 Cov.: 33 AF XY: 0.00000150 AC XY: 1 AN XY: 666930

African (AFR) AF: 0.00 AC: 0 AN: 26574

American (AMR) AF: 0.00 AC: 0 AN: 22482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22400

East Asian (EAS) AF: 0.00 AC: 0 AN: 31772

South Asian (SAS) AF: 0.00 AC: 0 AN: 71274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 0.00000282 AC: 3 AN: 1063092

Other (OTH) AF: 0.00 AC: 0 AN: 55436

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.081	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Uncertain	0.044	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.60
MutPred		0.28		Loss of catalytic residue at G6 (P = 0.041)
MVP		0.91
MPC		1.0
ClinPred		0.99	D
GERP RS		4.8
PromoterAI		-0.14	Neutral
Varity_R		0.50
gMVP		0.69
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs1600130570; hg19: chr19-48547163;