Genetic Variant NM_001306084.2:c.4539G>C (chr12-96644400-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001306084.2(CFAP54):c.4539G>C(p.Met1513Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,527,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CFAP54
NM_001306084.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0520

Publications

0 publications found

Variant links:

Genes affected

CFAP54 (HGNC:26456): (cilia and flagella associated protein 54) Predicted to be involved in cilium assembly; cilium movement involved in cell motility; and spermatogenesis. Predicted to act upstream of or within cerebrospinal fluid circulation; motile cilium assembly; and mucociliary clearance. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CFAP54 Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 54
Inheritance: AR Classification: STRONG Submitted by: ClinGen

CFAP54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02189833).

BP6

Variant 12-96644400-G-C is Benign according to our data. Variant chr12-96644400-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2672516.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306084.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP54	NM_001306084.2	MANE Select	c.4539G>C	p.Met1513Ile	missense	Exon 33 of 68	NP_001293013.1	Q96N23-1
	CFAP54	NM_001367885.1		c.4539G>C	p.Met1513Ile	missense	Exon 33 of 69	NP_001354814.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CFAP54	ENST00000524981.9	TSL:5 MANE Select	c.4539G>C	p.Met1513Ile	missense	Exon 33 of 68	ENSP00000431759.5	Q96N23-1
CFAP54	ENST00000637336.1	TSL:5	c.1254G>C	p.Met418Ile	missense	Exon 10 of 46	ENSP00000490000.1	A0A1B0GU80
CFAP54	ENST00000550977.2	TSL:5	c.777G>C	p.Met259Ile	missense	Exon 7 of 8	ENSP00000449035.2	H0YIB5

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000521

AC:

AN:

134240

AF XY:

0.0000274

show subpopulations

Gnomad AFR exome

AF:

0.000622

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.000485

GnomAD4 exome

AF:

0.0000371

AC:

AN:

1375594

Hom.:

Cov.:

AF XY:

0.0000368

AC XY:

AN XY:

679454

show subpopulations

African (AFR)

AF:

0.000955

AC:

AN:

31420

American (AMR)

AF:

0.00

AC:

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.0000398

AC:

AN:

25122

East Asian (EAS)

AF:

0.00

AC:

AN:

35682

South Asian (SAS)

AF:

0.0000127

AC:

AN:

79028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33882

Middle Eastern (MID)

AF:

0.000879

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000112

AC:

AN:

1071490

Other (OTH)

AF:

0.0000347

AC:

AN:

57598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000505

AC:

AN:

41570

American (AMR)

AF:

0.0000654

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000193

ExAC

AF:

0.0000648

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.3

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.43

M_CAP

Benign

0.0092

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

PhyloP100

0.052

PROVEAN

Benign

-0.16

REVEL

Benign

0.069

Sift

Benign

0.45

Sift4G

Benign

0.49

Vest4

0.050

MutPred

0.34

Gain of sheet (P = 0.039)

MVP

0.030

MPC

0.043

ClinPred

0.0024

GERP RS

-2.5

Varity_R

0.065

gMVP

0.044

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over