NM_194302.4:c.5718G>A

Variant names:

• chr2-219002997-C-T
• rs73089092
• NM_194302.4:c.5718G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_194302.4(CFAP65):​c.5718G>A​(p.Leu1906Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000728 in 1,561,940 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: CFAP65 NM_194302.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.112
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-219002997-C-T is Benign according to our data. Variant chr2-219002997-C-T is described in ClinVar as Benign. ClinVar VariationId is 780365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.112 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00374 (570/152334) while in subpopulation AFR AF = 0.0124 (516/41570). AF 95% confidence interval is 0.0115. There are 6 homozygotes in GnomAd4. There are 277 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.5718G>A	p.Leu1906Leu	synonymous	Exon 35 of 35	NP_919278.2	Q6ZU64-1
	CFAP65-AS1	NR_046086.1		n.86+697C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP65	ENST00000341552.10	TSL:5 MANE Select	c.5718G>A	p.Leu1906Leu	synonymous	Exon 35 of 35	ENSP00000340776.5	Q6ZU64-1
	CFAP65	ENST00000453220.5	TSL:5	c.5718G>A	p.Leu1906Leu	synonymous	Exon 33 of 33	ENSP00000409117.1	Q6ZU64-1
	ENSG00000224090	ENST00000441450.1	TSL:2	n.86+697C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00374 AC: 570 AN: 152216 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00115

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: 0.00334

GnomAD2 exomes AF: 0.00102 AC: 171 AN: 167954 AF XY: 0.000891

Gnomad AFR exome AF: 0.0125

Gnomad AMR exome AF: 0.000763

Gnomad ASJ exome AF: 0.000697

Gnomad EAS exome AF: 0.0000761

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000402 AC: 567 AN: 1409606 Hom.: 4 Cov.: 32 AF XY: 0.000346 AC XY: 241 AN XY: 695848

African (AFR) AF: 0.0118 AC: 387 AN: 32688

American (AMR) AF: 0.00100 AC: 36 AN: 35858

Ashkenazi Jewish (ASJ) AF: 0.000437 AC: 11 AN: 25190

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37618

South Asian (SAS) AF: 0.0000250 AC: 2 AN: 79982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49630

Middle Eastern (MID) AF: 0.000702 AC: 4 AN: 5702

European-Non Finnish (NFE) AF: 0.0000489 AC: 53 AN: 1084458

Other (OTH) AF: 0.00125 AC: 73 AN: 58480

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152334 Hom.: 6 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74490

African (AFR) AF: 0.0124 AC: 516 AN: 41570

American (AMR) AF: 0.00255 AC: 39 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68030

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.00268 Hom.: 1

Bravo AF: 0.00419

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.5
DANN	Benign	0.96
PhyloP100		-0.11
Mutation Taster		=100/0	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: rs73089092; hg19: chr2-219867719;