Genetic Variant CFAP96:p.Asp171Glu (chr4-185436338-T-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001114357.3(CFAP96):c.513T>G(p.Asp171Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,549,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

CFAP96
NM_001114357.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.131

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08646357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP96	NM_001114357.3 link	c.513T>G	p.Asp171Glu	missense_variant	Exon 5 of 8	ENST00000378850.5	NP_001107829.1	A7E2U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
C4orf47	ENST00000378850.5 link	c.513T>G	p.Asp171Glu	missense_variant	Exon 5 of 8	1	NM_001114357.3	ENSP00000368127.4	A7E2U8
C4orf47	ENST00000511581.5 link	c.513T>G	p.Asp171Glu	missense_variant	Exon 5 of 5	3		ENSP00000423127.1	D6R9T4
C4orf47	ENST00000508698.3 link	n.*127+155T>G		intron_variant	Intron 3 of 5	5		ENSP00000425418.1	D6RB10
C4orf47	ENST00000511138.5 link	c.*28T>G		downstream_gene_variant		3		ENSP00000422279.1	D6RCA9

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000195

AC:

AN:

153952

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.000462

GnomAD4 exome

AF:

0.00000859

AC:

AN:

1397614

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

689488

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

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:

0.00000186

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.513T>G (p.D171E) alteration is located in exon 4 (coding exon 4) of the C4orf47 gene. This alteration results from a T to G substitution at nucleotide position 513, causing the aspartic acid (D) at amino acid position 171 to be replaced by a glutamic acid (E). 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

0.29

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.023

Sift

Benign

0.094

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.41

.;B

Vest4

0.20

MutPred

0.25

Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);

MVP

0.030

ClinPred

0.059

GERP RS

0.57

Varity_R

0.062

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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