9-127710601-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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

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]

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

ACMG classification

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	UniProt
CFAP157	NM_001012502.3	c.434G>T	p.Gly145Val	missense_variant, splice_region_variant	3/9	ENST00000373295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP157	ENST00000373295.7	c.434G>T	p.Gly145Val	missense_variant, splice_region_variant	3/9	5	NM_001012502.3	P2
PTRH1	ENST00000335223.5	c.205+4834C>A		intron_variant		1
CFAP157	ENST00000614677.1	c.434G>T	p.Gly145Val	missense_variant, splice_region_variant	3/9	2		A2
CFAP157	ENST00000496009.5	n.477-80G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152252 Hom.: 0 Cov.: 32

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: 13 AN: 193026 Hom.: 0 AF XY: 0.0000769 AC XY: 8 AN XY: 104086

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: 73 AN: 1427594 Hom.: 0 Cov.: 31 AF XY: 0.0000453 AC XY: 32 AN XY: 706928

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: 6 AN: 152252 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74388

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.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000334 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.012
Eigen_PC	Benign	-0.069
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	D
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	D
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

Other links and lift over

dbSNP: rs202023603; hg19: chr9-130472880;