chr9-127710601-G-T

Position:

chr9-127710601-G-T

Variant summary

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

The NM_001012502.3(CFAP157):c.434G>T(p.Gly145Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00005 in 1,579,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

CFAP157
NM_001012502.3 missense, splice_region

Scores

Splicing: ADA: 0.8894

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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:

CFAP157 (HGNC:):

CFAP157 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=0.24059507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP157	NM_001012502.3 linkuse as main transcript	c.434G>T	p.Gly145Val	missense_variant, splice_region_variant	3/9	ENST00000373295.7	NP_001012520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CFAP157	ENST00000373295.7 linkuse as main transcript	c.434G>T	p.Gly145Val	missense_variant, splice_region_variant	3/9	5	NM_001012502.3	ENSP00000362392.1	Q5JU67-1
PTRH1	ENST00000335223.5 linkuse as main transcript	c.205+4834C>A		intron_variant		1		ENSP00000493136.1	A0A286YF52
CFAP157	ENST00000614677.1 linkuse as main transcript	c.434G>T	p.Gly145Val	missense_variant, splice_region_variant	3/9	2		ENSP00000478313.1	Q5JU67-2
CFAP157	ENST00000496009.5 linkuse as main transcript	n.477-80G>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152252

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000673

AC:

AN:

193026

Hom.:

AF XY:

0.0000769

AC XY:

AN XY:

104086

show subpopulations

Gnomad AFR exome

AF:

0.000180

Gnomad AMR exome

AF:

0.0000352

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000395

Gnomad FIN exome

AF:

0.0000592

Gnomad NFE exome

AF:

0.0000844

Gnomad OTH exome

AF:

0.000202

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1427594

Hom.:

Cov.:

AF XY:

0.0000453

AC XY:

AN XY:

706928

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.0000762

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000490

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.0000475

Gnomad4 OTH exome

AF:

0.0000678

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74388

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000262

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000334

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

Jul 28, 2021

The c.434G>T (p.G145V) alteration is located in exon 3 (coding exon 3) of the CFAP157 gene. This alteration results from a G to T substitution at nucleotide position 434, causing the glycine (G) at amino acid position 145 to be replaced by a valine (V). 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

0.22

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.069

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.97

PROVEAN

Uncertain

-4.0

D;.

REVEL

Benign

0.15

Sift

Uncertain

0.012

D;.

Sift4G

Uncertain

0.032

D;D

Polyphen

0.98

D;.

Vest4

0.15

MutPred

0.25

Gain of catalytic residue at G145 (P = 0.0319);Gain of catalytic residue at G145 (P = 0.0319);

MVP

0.53

MPC

0.47

ClinPred

0.51

GERP RS

0.17

Varity_R

0.19

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Benign

0.63

SpliceAI score (max)

0.12

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