12-121921490-G-A

Position:

• chr12-121921490-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_144668.6(CFAP251):​c.185G>A​(p.Gly62Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: CFAP251 NM_144668.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.98

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022441924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.185G>A	p.Gly62Glu	missense_variant	2/22	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.185G>A	p.Gly62Glu	missense_variant	2/18		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.185G>A	p.Gly62Glu	missense_variant	2/22	1	NM_144668.6	ENSP00000288912
CFAP251	ENST00000397454.2	c.185G>A	p.Gly62Glu	missense_variant	2/18	1		ENSP00000380595	P1
CFAP251	ENST00000540779.1	n.83G>A		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000565 AC: 2 AN: 35426 Hom.: 0 AF XY: 0.000108 AC XY: 2 AN XY: 18492

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000153

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.000219 Hom.: 0

Bravo AF: 0.000136

ExAC AF: 0.0000167 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0020
DANN	Benign	0.72
DEOGEN2	Benign	0.0040	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00053	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.022	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.18	T
PROVEAN	Benign	0.21	N;N
REVEL	Benign	0.021
Sift	Benign	1.0	T;T
Sift4G	Benign	0.54	T;T
Polyphen		0.0	B;.
Vest4		0.10
MVP		0.014
MPC		0.17
ClinPred		0.042	T
GERP RS		-1.4
Varity_R		0.042
gMVP		0.027

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: rs58415126; hg19: chr12-122359396; COSMIC: COSV55838893; COSMIC: COSV55838893;