9-127709578-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012502.3(CFAP157):c.318G>C(p.Gln106His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP157 NM_001012502.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0580

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=0.21823156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP157	NM_001012502.3	c.318G>C	p.Gln106His	missense_variant	2/9	ENST00000373295.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP157	ENST00000373295.7	c.318G>C	p.Gln106His	missense_variant	2/9	5	NM_001012502.3	P2
PTRH1	ENST00000335223.5	c.205+5857C>G		intron_variant		1
CFAP157	ENST00000614677.1	c.318G>C	p.Gln106His	missense_variant	2/9	2		A2
CFAP157	ENST00000496009.5	n.361G>C		non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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 11, 2023

The c.318G>C (p.Q106H) alteration is located in exon 2 (coding exon 2) of the CFAP157 gene. This alteration results from a G to C substitution at nucleotide position 318, causing the glutamine (Q) at amino acid position 106 to be replaced by a histidine (H). 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	Uncertain	0.34
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	8.0
Dann	Uncertain	0.99
DEOGEN2	Benign	0.063	T;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.61	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.99	N
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.10
Sift	Benign	0.055	T;.
Sift4G	Benign	0.45	T;T
Polyphen		0.82	P;.
Vest4		0.37
MutPred		0.21		Loss of disorder (P = 0.0945);Loss of disorder (P = 0.0945);
MVP		0.24
MPC		0.79
ClinPred		0.95	D
GERP RS		-1.1
Varity_R		0.13
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-130471857;