Variant 9-127709574-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001012502.3(CFAP157):c.314T>C(p.Leu105Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CFAP157
NM_001012502.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.54

Variant links:

Genes affected

CFAP157 (HGNC:27843): (cilia and flagella associated protein 157) Predicted to enable microtubule binding activity. Predicted to be involved in sperm axoneme assembly. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CFAP157 links:

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PTRH1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP157	NM_001012502.3 linkuse as main transcript	c.314T>C	p.Leu105Pro	missense_variant	2/9	ENST00000373295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP157	ENST00000373295.7 linkuse as main transcript	c.314T>C	p.Leu105Pro	missense_variant	2/9	5	NM_001012502.3	P2	Q5JU67-1
PTRH1	ENST00000335223.5 linkuse as main transcript	c.205+5861A>G		intron_variant		1
CFAP157	ENST00000614677.1 linkuse as main transcript	c.314T>C	p.Leu105Pro	missense_variant	2/9	2		A2	Q5JU67-2
CFAP157	ENST00000496009.5 linkuse as main transcript	n.357T>C		non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249468

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135374

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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:

0.0000564

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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 22, 2022

The c.314T>C (p.L105P) alteration is located in exon 2 (coding exon 2) of the CFAP157 gene. This alteration results from a T to C substitution at nucleotide position 314, causing the leucine (L) at amino acid position 105 to be replaced by a proline (P). 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

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.38

T;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.67

T;T

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Benign

-0.56

MutationTaster

Benign

1.0

PROVEAN

Pathogenic

-6.2

D;.

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

D;.

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.85

MutPred

0.31

Loss of stability (P = 0.0567);Loss of stability (P = 0.0567);

MVP

0.64

MPC

1.0

ClinPred

0.98

GERP RS

5.1

Varity_R

0.93

gMVP

0.88

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