NM_194302.4:c.3939C>T

Variant names:

• chr2-219013277-G-A
• rs151066400
• NM_194302.4:c.3939C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_194302.4(CFAP65):​c.3939C>T​(p.Asp1313Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,613,224 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (2 hom.)
• Consequence: CFAP65 NM_194302.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.813
• Publications: 1 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-219013277-G-A is Benign according to our data. Variant chr2-219013277-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2651904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.813 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00205 (312/152336) while in subpopulation AFR AF = 0.00654 (272/41568). AF 95% confidence interval is 0.0059. There are 1 homozygotes in GnomAd4. There are 156 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.3939C>T	p.Asp1313Asp	synonymous	Exon 24 of 35	NP_919278.2	Q6ZU64-1
	CFAP65-AS1	NR_046086.1		n.173-625G>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.3939C>T	p.Asp1313Asp	synonymous	Exon 24 of 35	ENSP00000340776.5	Q6ZU64-1
	CFAP65	ENST00000453220.5	TSL:5	c.3939C>T	p.Asp1313Asp	synonymous	Exon 22 of 33	ENSP00000409117.1	Q6ZU64-1
	ENSG00000224090	ENST00000441450.1	TSL:2	n.173-625G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 312 AN: 152218 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00656

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

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: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000551 AC: 138 AN: 250284 AF XY: 0.000495

Gnomad AFR exome AF: 0.00563

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000133

Gnomad OTH exome AF: 0.000981

GnomAD4 exome AF: 0.000229 AC: 334 AN: 1460888 Hom.: 2 Cov.: 31 AF XY: 0.000205 AC XY: 149 AN XY: 726776

African (AFR) AF: 0.00538 AC: 180 AN: 33462

American (AMR) AF: 0.000672 AC: 30 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.000459 AC: 12 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5754

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111286

Other (OTH) AF: 0.000928 AC: 56 AN: 60358

GnomAD4 genome AF: 0.00205 AC: 312 AN: 152336 Hom.: 1 Cov.: 32 AF XY: 0.00209 AC XY: 156 AN XY: 74478

African (AFR) AF: 0.00654 AC: 272 AN: 41568

American (AMR) AF: 0.00176 AC: 27 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00157 Hom.: 0

Bravo AF: 0.00233

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.9
DANN	Benign	0.61
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs151066400; hg19: chr2-219877999;