Genetic Variant CFAP96:p.Ser254Cys (chr4-185445010-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001114357.3(CFAP96):c.761C>G(p.Ser254Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000406 in 1,551,456 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 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CFAP96
NM_001114357.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

Variant links:

Genes affected

CFAP96 (HGNC:34346): (cilia and flagella associated protein 96) Located in 9+0 non-motile cilium; centrosome; and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

CFAP96 links:

CCDC110 (HGNC:28504): (coiled-coil domain containing 110) Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CCDC110 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32969534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP96	NM_001114357.3 link	c.761C>G	p.Ser254Cys	missense_variant	Exon 7 of 8	ENST00000378850.5	NP_001107829.1	A7E2U8
CCDC110	NM_152775.4 link	c.*492G>C		downstream_gene_variant		ENST00000307588.8	NP_689988.1	Q8TBZ0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C4orf47	ENST00000378850.5 link	c.761C>G	p.Ser254Cys	missense_variant	Exon 7 of 8	1	NM_001114357.3	ENSP00000368127.4		A7E2U8
CCDC110	ENST00000307588.8 link	c.*492G>C		downstream_gene_variant		1	NM_152775.4	ENSP00000306776.3		Q8TBZ0-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000714

AC:

AN:

154018

Hom.:

AF XY:

0.0000857

AC XY:

AN XY:

81722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000324

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:

0.0000503

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000336

AC:

AN:

1399298

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

690152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000420

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000406

Gnomad4 NFE exome

AF:

0.0000222

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.000105

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000786

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000449

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.761C>G (p.S254C) alteration is located in exon 6 (coding exon 6) of the C4orf47 gene. This alteration results from a C to G substitution at nucleotide position 761, causing the serine (S) at amino acid position 254 to be replaced by a cysteine (C). 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

Benign

0.25

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.020

MetaRNN

Benign

0.33

MetaSVM

Uncertain

0.10

MutationAssessor

Pathogenic

3.1

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.45

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.37

MVP

0.18

ClinPred

0.71

GERP RS

5.7

Varity_R

0.26

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over