Variant 2-219009381-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_194302.4(CFAP65):c.4532A>G(p.His1511Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CFAP65
NM_194302.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

CFAP65 (HGNC:25325): (cilia and flagella associated protein 65) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. The chicken ortholog of this gene is involved in the Rose-comb mutation, which is a large chromosome inversion, resulting in altered comb morphology and defects in sperm motility. [provided by RefSeq, Aug 2016]

CFAP65 links:

(HGNC:):

links:

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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=0.10993862).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP65	NM_194302.4 linkuse as main transcript	c.4532A>G	p.His1511Arg	missense_variant	28/35	ENST00000341552.10	NP_919278.2
LOC100129175	NR_046086.1 linkuse as main transcript	n.87-576T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP65	ENST00000341552.10 linkuse as main transcript	c.4532A>G	p.His1511Arg	missense_variant	28/35	5	NM_194302.4	ENSP00000340776	A2	Q6ZU64-1
	ENST00000441450.1 linkuse as main transcript	n.87-576T>C		intron_variant, non_coding_transcript_variant		2
CFAP65	ENST00000453220.5 linkuse as main transcript	c.4532A>G	p.His1511Arg	missense_variant	26/33	5		ENSP00000409117	A2	Q6ZU64-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460424

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.4532A>G (p.H1511R) alteration is located in exon 28 (coding exon 26) of the CFAP65 gene. This alteration results from a A to G substitution at nucleotide position 4532, causing the histidine (H) at amino acid position 1511 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.024

T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.60

.;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.95

N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.11

Sift

Benign

0.71

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0020

B;B

Vest4

0.32

MutPred

0.45

Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);

MVP

0.28

MPC

0.088

ClinPred

0.092

GERP RS

5.5

Varity_R

0.067

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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