Variant 2-169650517-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001085447.2(CFAP210):c.964A>T(p.Met322Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,558,612 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: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

CFAP210
NM_001085447.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

CFAP210 (HGNC:25064): (cilia and flagella associated protein 210)

CFAP210 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05293989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFAP210	NM_001085447.2 linkuse as main transcript	c.964A>T	p.Met322Leu	missense_variant	7/9	ENST00000447353.6	NP_001078916.1
CFAP210	XM_047443326.1 linkuse as main transcript	c.892A>T	p.Met298Leu	missense_variant	8/10		XP_047299282.1
CFAP210	XM_011510590.2 linkuse as main transcript	c.721A>T	p.Met241Leu	missense_variant	7/9		XP_011508892.1
CFAP210	XM_047443327.1 linkuse as main transcript	c.667A>T	p.Met223Leu	missense_variant	6/8		XP_047299283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP210	ENST00000447353.6 linkuse as main transcript	c.964A>T	p.Met322Leu	missense_variant	7/9	1	NM_001085447.2	ENSP00000391504	P1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000103

AC:

AN:

194444

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

105790

show subpopulations

Gnomad AFR exome

AF:

0.0000768

Gnomad AMR exome

AF:

0.0000933

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:

0.000173

Gnomad OTH exome

AF:

0.000220

GnomAD4 exome

AF:

0.000201

AC:

282

AN:

1406308

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

132

AN XY:

697516

show subpopulations

Gnomad4 AFR exome

AF:

0.0000978

Gnomad4 AMR exome

AF:

0.000125

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:

0.000248

Gnomad4 OTH exome

AF:

0.0000691

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000569

Hom.:

Bravo

AF:

0.000181

ExAC

AF:

0.0000912

AC:

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 14, 2021

The c.964A>T (p.M322L) alteration is located in exon 7 (coding exon 7) of the CCDC173 gene. This alteration results from a A to T substitution at nucleotide position 964, causing the methionine (M) at amino acid position 322 to be replaced by a leucine (L). 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

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.58

M_CAP

Benign

0.0075

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

0.81

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.72

REVEL

Benign

0.078

Sift

Benign

0.51

Sift4G

Benign

0.32

Polyphen

0.44

Vest4

0.29

MutPred

0.40

Loss of methylation at K324 (P = 0.0632);

MVP

0.040

MPC

0.056

ClinPred

0.038

GERP RS

3.0

Varity_R

0.086

gMVP

0.14

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

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