NM_019855.5:c.22G>T

Variant names:

• chr19-48043901-C-A
• rs756797217
• NM_019855.5:c.22G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019855.5(CABP5):​c.22G>T​(p.Ala8Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000148 in 1,347,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. A8T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: CABP5 NM_019855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29503816).

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.22G>T	p.Ala8Ser	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.22G>T	p.Ala8Ser	missense	Exon 1 of 6	ENSP00000293255.1	Q9NP86
	CABP5	ENST00000602032.1	TSL:3	n.-20G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000608 AC: 1 AN: 164350 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000120

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1347804 Hom.: 0 Cov.: 33 AF XY: 0.00000301 AC XY: 2 AN XY: 665130

African (AFR) AF: 0.00 AC: 0 AN: 26462

American (AMR) AF: 0.00 AC: 0 AN: 21762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22228

East Asian (EAS) AF: 0.00 AC: 0 AN: 31732

South Asian (SAS) AF: 0.00 AC: 0 AN: 70644

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5400

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1061902

Other (OTH) AF: 0.00 AC: 0 AN: 55300

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.0090	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.0
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.81	P
Vest4		0.41
MutPred		0.20		Gain of phosphorylation at A8 (P = 0.054)
MVP		0.77
MPC		0.27
ClinPred		0.88	D
GERP RS		4.9
PromoterAI		-0.12	Neutral
Varity_R		0.16
gMVP		0.57
Mutation Taster		=78/22	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: rs756797217; hg19: chr19-48547158;