10-73275466-C-T

Variant names:

• chr10-73275466-C-T
• rs369158199
• NM_001367801.1:c.2863G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001367801.1(CFAP70):​c.2863G>A​(p.Ala955Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A955S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP70 NM_001367801.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.41
• Publications: 0 publications found

Genes affected

CFAP70 (HGNC:30726): (cilia and flagella associated protein 70) Predicted to be involved in cilium assembly and cilium movement. Located in ciliary basal body and sperm flagellum. Part of outer dynein arm. Implicated in spermatogenic failure 41. [provided by Alliance of Genome Resources, Apr 2022]

DNAJC9-AS1 (HGNC:31432): (DNAJC9 and MRPS16 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367801.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP70	NM_001367801.1	MANE Select	c.2863G>A	p.Ala955Thr	missense	Exon 23 of 28	NP_001354730.1	A0A087WSW1
	CFAP70	NM_001350933.2		c.2653G>A	p.Ala885Thr	missense	Exon 22 of 27	NP_001337862.1	A0A8J8YUN0
	CFAP70	NM_001350934.2		c.2287G>A	p.Ala763Thr	missense	Exon 21 of 26	NP_001337863.1	A0A8I5KZ08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP70	ENST00000355577.9	TSL:5 MANE Select	c.2863G>A	p.Ala955Thr	missense	Exon 23 of 28	ENSP00000347781.4	A0A087WSW1
	DNAJC9-AS1	ENST00000440197.2	TSL:1	n.1347C>T		non_coding_transcript_exon	Exon 4 of 4
	CFAP70	ENST00000310715.8	TSL:5	c.2653G>A	p.Ala885Thr	missense	Exon 22 of 27	ENSP00000310829.4	A0A8J8YUN0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243038 AF XY: 0.00

Gnomad AFR exome AF: 0.0000630

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.68	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.74	D
MetaSVM	Uncertain	-0.090	T
PhyloP100		5.4
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0070	D
Polyphen		1.0	D
Vest4		0.71
MVP		0.68
MPC		0.84
ClinPred		0.92	D
GERP RS		5.9
Varity_R		0.47
gMVP		0.42
Mutation Taster		=59/41	polymorphism

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

Other links and lift over

dbSNP: rs369158199; hg19: chr10-75035224;