dbSNP rs199734613: CFAP97:p.Glu431Gln (chr4-185175815-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020827.3(CFAP97):c.1291G>C(p.Glu431Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000167 in 1,613,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CFAP97
NM_020827.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Publications

2 publications found

Variant links:

Genes affected

CFAP97 (HGNC:29276): (cilia and flagella associated protein 97)

CFAP97 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06832445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP97	NM_020827.3 link	c.1291G>C	p.Glu431Gln	missense_variant	Exon 3 of 5	ENST00000458385.7	NP_065878.1	Q9P2B7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP97	ENST00000458385.7 link	c.1291G>C	p.Glu431Gln	missense_variant	Exon 3 of 5	2	NM_020827.3	ENSP00000409964.2	Q9P2B7-1
CFAP97	ENST00000514798.1 link	c.1291G>C	p.Glu431Gln	missense_variant	Exon 3 of 4	1		ENSP00000423312.1	Q9P2B7-2
CFAP97	ENST00000502992.1 link	n.579G>C		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152058

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:

0.00154

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000757

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000205

AC:

AN:

248640

AF XY:

0.000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.000743

Gnomad NFE exome

AF:

0.0000976

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000163

AC:

238

AN:

1461314

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

127

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000448

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00345

AC:

137

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86106

European-Finnish (FIN)

AF:

0.000805

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1111724

Other (OTH)

AF:

0.0000994

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000210

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00154

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000757

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000366

AC:

ExAC

AF:

0.000207

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1291G>C (p.E431Q) alteration is located in exon 3 (coding exon 2) of the CFAP97 gene. This alteration results from a G to C substitution at nucleotide position 1291, causing the glutamic acid (E) at amino acid position 431 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.041

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-0.70

PhyloP100

5.2

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.21

Sift

Benign

0.051

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.27

MVP

0.73

MPC

0.13

ClinPred

0.089

GERP RS

6.2

Varity_R

0.14

gMVP

0.60

Mutation Taster

=50/50

(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

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rs199734613

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over