2-219010669-C-A

Variant names:

• chr2-219010669-C-A
• rs778237584
• NM_194302.4:c.4185G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_194302.4(CFAP65):​c.4185G>T​(p.Ser1395Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S1395S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CFAP65 NM_194302.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.87
• Publications: 0 publications found

Genes affected

CFAP65 (HGNC:25325): (cilia and flagella associated protein 65) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. The chicken ortholog of this gene is involved in the Rose-comb mutation, which is a large chromosome inversion, resulting in altered comb morphology and defects in sperm motility. [provided by RefSeq, Aug 2016]

CFAP65 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 40

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000224090 (HGNC:58353):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-3.87 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194302.4. 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
	CFAP65	NM_194302.4	MANE Select	c.4185G>T	p.Ser1395Ser	synonymous	Exon 26 of 35	NP_919278.2	Q6ZU64-1
	CFAP65-AS1	NR_046086.1		n.172+627C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP65	ENST00000341552.10	TSL:5 MANE Select	c.4185G>T	p.Ser1395Ser	synonymous	Exon 26 of 35	ENSP00000340776.5	Q6ZU64-1
	CFAP65	ENST00000453220.5	TSL:5	c.4185G>T	p.Ser1395Ser	synonymous	Exon 24 of 33	ENSP00000409117.1	Q6ZU64-1
	ENSG00000224090	ENST00000441450.1	TSL:2	n.172+627C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458004 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725098

African (AFR) AF: 0.0000899 AC: 3 AN: 33352

American (AMR) AF: 0.00 AC: 0 AN: 43994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 85576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110766

Other (OTH) AF: 0.00 AC: 0 AN: 60222

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.54
DANN	Benign	0.76
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs778237584; hg19: chr2-219875391;