rs1554800117

Variant names:

• chr9-133468580-A-C
• rs1554800117
• NM_017586.5:c.446A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-133468580-A-C
• chr9-133468580-A-G
• chr9-133468580-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017586.5(CACFD1):​c.446A>C​(p.Tyr149Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,434,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. Y149F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CACFD1 NM_017586.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63
• Publications: 0 publications found

Genes affected

CACFD1 (HGNC:1365): (calcium channel flower domain containing 1) Predicted to be involved in vesicle-mediated transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902295 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16838127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACFD1	NM_017586.5	c.446A>C	p.Tyr149Ser	missense_variant	Exon 5 of 5	ENST00000316948.9	NP_060056.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACFD1	ENST00000316948.9	c.446A>C	p.Tyr149Ser	missense_variant	Exon 5 of 5	1	NM_017586.5	ENSP00000317121.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1434564 Hom.: 0 Cov.: 32 AF XY: 0.00000281 AC XY: 2 AN XY: 710756

African (AFR) AF: 0.00 AC: 0 AN: 33314

American (AMR) AF: 0.00 AC: 0 AN: 39748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25490

East Asian (EAS) AF: 0.00 AC: 0 AN: 38864

South Asian (SAS) AF: 0.00 AC: 0 AN: 81674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000182 AC: 2 AN: 1100550

Other (OTH) AF: 0.0000168 AC: 1 AN: 59592

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	23
DANN	Benign	0.77
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.32	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.83	T
PhyloP100		7.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.17	N;N
REVEL	Benign	0.24
Sift	Benign	0.15	T;T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.24
MutPred		0.19		.;Loss of methylation at R188 (P = 0.1201);
MVP		0.20
MPC		0.11
ClinPred		0.94	D
GERP RS		4.6
Varity_R		0.50
gMVP		0.056
Mutation Taster		=55/45	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: rs1554800117; hg19: chr9-136333702;