10-73275466-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001367801.1(CFAP70):​c.2863G>T​(p.Ala955Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP70 NM_001367801.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

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

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>T	p.Ala955Ser	missense	Exon 23 of 28	NP_001354730.1	A0A087WSW1
	CFAP70	NM_001350933.2		c.2653G>T	p.Ala885Ser	missense	Exon 22 of 27	NP_001337862.1	A0A8J8YUN0
	CFAP70	NM_001350934.2		c.2287G>T	p.Ala763Ser	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>T	p.Ala955Ser	missense	Exon 23 of 28	ENSP00000347781.4	A0A087WSW1
	DNAJC9-AS1	ENST00000440197.2	TSL:1	n.1347C>A		non_coding_transcript_exon	Exon 4 of 4
	CFAP70	ENST00000310715.8	TSL:5	c.2653G>T	p.Ala885Ser	missense	Exon 22 of 27	ENSP00000310829.4	A0A8J8YUN0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1454576 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 723418

African (AFR) AF: 0.00 AC: 0 AN: 32974

American (AMR) AF: 0.00 AC: 0 AN: 43394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39322

South Asian (SAS) AF: 0.00 AC: 0 AN: 84466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109416

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	-0.060	T
PhyloP100		5.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.45
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.57		Gain of disorder (P = 0.0391)
MVP		0.67
MPC		0.38
ClinPred		0.93	D
GERP RS		5.9
Varity_R		0.45
gMVP		0.31
Mutation Taster		=47/53	disease causing

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;