NM_001367801.1:c.3244C>T

Variant names:

• chr10-73256410-G-A
• rs748363705
• NM_001367801.1:c.3244C>T

Variant summary

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

The NM_001367801.1(CFAP70):​c.3244C>T​(p.Arg1082Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1082Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: CFAP70 NM_001367801.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10
• Publications: 1 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, 0.748

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.3244C>T	p.Arg1082Trp	missense	Exon 27 of 28	NP_001354730.1	A0A087WSW1
	CFAP70	NM_001350933.2		c.3034C>T	p.Arg1012Trp	missense	Exon 26 of 27	NP_001337862.1	A0A8J8YUN0
	CFAP70	NM_001350934.2		c.2668C>T	p.Arg890Trp	missense	Exon 25 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.3244C>T	p.Arg1082Trp	missense	Exon 27 of 28	ENSP00000347781.4	A0A087WSW1
	DNAJC9-AS1	ENST00000440197.2	TSL:1	n.182+7960G>A		intron	N/A
	CFAP70	ENST00000310715.8	TSL:5	c.3034C>T	p.Arg1012Trp	missense	Exon 26 of 27	ENSP00000310829.4	A0A8J8YUN0

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 151986 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251416 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000328 AC: 48 AN: 1461808 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000360 AC: 40 AN: 1111960

Other (OTH) AF: 0.0000828 AC: 5 AN: 60394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151986 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74236

African (AFR) AF: 0.00 AC: 0 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.000109

EpiControl AF: 0.000119

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	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.16	T
PhyloP100		1.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.50		Loss of disorder (P = 0.0649)
MVP		0.51
MPC		1.0
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.74
gMVP		0.57
Mutation Taster		=72/28	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: rs748363705; hg19: chr10-75016168; COSMIC: COSV60284112; COSMIC: COSV60284112;