chr12-121921475-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_144668.6(CFAP251):c.170C>T(p.Thr57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000798 in 614,268 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000071 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000081 ( 1 hom. )

Consequence

CFAP251
NM_144668.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.83

Publications

3 publications found

Variant links:

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]

CFAP251 Gene-Disease associations (from GenCC):

spermatogenic failure 33
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CFAP251 links:

ENSG00000256950 (HGNC:):

ENSG00000256950 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011632621).

BP6

Variant 12-121921475-C-T is Benign according to our data. Variant chr12-121921475-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3143401.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144668.6. 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
	CFAP251	NM_144668.6	MANE Select	c.170C>T	p.Thr57Met	missense	Exon 2 of 22	NP_653269.3	Q8TBY9-1
	CFAP251	NM_001178003.2		c.170C>T	p.Thr57Met	missense	Exon 2 of 18	NP_001171474.1	Q8TBY9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP251	ENST00000288912.9	TSL:1 MANE Select	c.170C>T	p.Thr57Met	missense	Exon 2 of 22	ENSP00000288912.4	Q8TBY9-1
CFAP251	ENST00000397454.2	TSL:1	c.170C>T	p.Thr57Met	missense	Exon 2 of 18	ENSP00000380595.2	Q8TBY9-2
CFAP251	ENST00000880754.1		c.170C>T	p.Thr57Met	missense	Exon 2 of 22	ENSP00000550813.1

Frequencies

GnomAD3 genomes

AF:

0.0000710

AC:

AN:

70468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000840

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00877

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000907

AC:

AN:

231594

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000809

AC:

AN:

543744

Hom.:

Cov.:

AF XY:

0.0000937

AC XY:

AN XY:

277558

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10908

American (AMR)

AF:

0.00

AC:

AN:

22056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11716

East Asian (EAS)

AF:

0.000452

AC:

AN:

26552

South Asian (SAS)

AF:

0.000331

AC:

AN:

39248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2004

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

369176

Other (OTH)

AF:

0.000311

AC:

AN:

25736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000709

AC:

AN:

70524

Hom.:

Cov.:

AF XY:

0.0000586

AC XY:

AN XY:

34108

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16778

American (AMR)

AF:

0.00

AC:

AN:

7602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1612

East Asian (EAS)

AF:

0.000840

AC:

AN:

2380

South Asian (SAS)

AF:

0.00

AC:

AN:

2160

European-Finnish (FIN)

AF:

0.000192

AC:

AN:

5220

Middle Eastern (MID)

AF:

0.00962

AC:

AN:

104

European-Non Finnish (NFE)

AF:

0.0000300

AC:

AN:

33278

Other (OTH)

AF:

0.00

AC:

AN:

1018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000283

Hom.:

ExAC

AF:

0.0000744

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0070

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0030

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0055

LIST_S2

Benign

0.43

M_CAP

Benign

0.00051

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.98

PhyloP100

-1.8

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.24

REVEL

Benign

0.011

Sift

Benign

0.13

Sift4G

Benign

0.080

Polyphen

0.0

Vest4

0.12

MVP

0.030

MPC

0.13

ClinPred

0.024

GERP RS

-4.8

Varity_R

0.018

gMVP

0.058

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over