chr12-121921619-C-A

Variant names:

• chr12-121921619-C-A
• NM_144668.6:c.314C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144668.6(CFAP251):​c.314C>A​(p.Ala105Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP251 NM_144668.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ENSG00000256950 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025879204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.314C>A	p.Ala105Glu	missense_variant	Exon 2 of 22	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.314C>A	p.Ala105Glu	missense_variant	Exon 2 of 18		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.314C>A	p.Ala105Glu	missense_variant	Exon 2 of 22	1	NM_144668.6	ENSP00000288912.4
ENSG00000256950	ENST00000546333.1	n.*419C>A		downstream_gene_variant		5		ENSP00000477146.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461692 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.011
DANN	Benign	0.54
DEOGEN2	Benign	0.0024	T;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00033	N
LIST_S2	Benign	0.19	T;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.026	T;T
MetaSVM	Benign	-0.98	T
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.41	N;N
REVEL	Benign	0.0030
Sift	Benign	1.0	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.0	B;.
Vest4		0.034
MutPred		0.21		Gain of catalytic residue at V103 (P = 0.0044);Gain of catalytic residue at V103 (P = 0.0044);
MVP		0.092
MPC		0.15
ClinPred		0.038	T
GERP RS		-3.0
Varity_R		0.066
gMVP		0.070

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122359525;