NM_001012502.3:c.10A>G

Variant names:

• chr9-127707041-A-G
• rs765972226
• NM_001012502.3:c.10A>G

Variant summary

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

The NM_001012502.3(CFAP157):​c.10A>G​(p.Lys4Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CFAP157 NM_001012502.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP157	NM_001012502.3	c.10A>G	p.Lys4Glu	missense_variant	Exon 1 of 9	ENST00000373295.7	NP_001012520.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP157	ENST00000373295.7	c.10A>G	p.Lys4Glu	missense_variant	Exon 1 of 9	5	NM_001012502.3	ENSP00000362392.1
PTRH1	ENST00000335223.5	c.205+8394T>C		intron_variant	Intron 1 of 2	1		ENSP00000493136.1
CFAP157	ENST00000614677.1	c.10A>G	p.Lys4Glu	missense_variant	Exon 1 of 9	2		ENSP00000478313.1
CFAP157	ENST00000496009.5	n.53A>G		non_coding_transcript_exon_variant	Exon 1 of 8	2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461418 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.059	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	-0.12	T
PROVEAN	Uncertain	-3.1	D;.
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;T
Polyphen		1.0	D;.
Vest4		0.54
MutPred		0.22		Loss of methylation at K4 (P = 0.0014);Loss of methylation at K4 (P = 0.0014);
MVP		0.83
MPC		0.57
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.57

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

Other links and lift over

dbSNP: rs765972226; hg19: chr9-130469320;