chr7-90245460-C-T

Variant names:

• chr7-90245460-C-T
• rs17865323
• NM_001039706.3:c.36C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001039706.3(CFAP69):​c.36C>T​(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,556,230 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (76 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (48 hom.)
• Consequence: CFAP69 NM_001039706.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.68
• Publications: 0 publications found

Genes affected

CFAP69 (HGNC:26107): (cilia and flagella associated protein 69) Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Apr 2022]

CFAP69 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 24

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000289836 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 7-90245460-C-T is Benign according to our data. Variant chr7-90245460-C-T is described in ClinVar as Benign. ClinVar VariationId is 768178.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.68 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039706.3. 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
	CFAP69	NM_001039706.3	MANE Select	c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 22	NP_001350367.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP69	ENST00000389297.8	TSL:1 MANE Select	c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.36C>T	p.Ala12Ala	synonymous	Exon 1 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2286 AN: 152092 Hom.: 75 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00314 AC: 608 AN: 193570 AF XY: 0.00236

Gnomad AFR exome AF: 0.0496

Gnomad AMR exome AF: 0.00192

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000773

Gnomad OTH exome AF: 0.00292

GnomAD4 exome AF: 0.00131 AC: 1839 AN: 1404020 Hom.: 48 Cov.: 31 AF XY: 0.00111 AC XY: 772 AN XY: 697762

African (AFR) AF: 0.0523 AC: 1504 AN: 28750

American (AMR) AF: 0.00240 AC: 85 AN: 35410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23962

East Asian (EAS) AF: 0.00 AC: 0 AN: 33232

South Asian (SAS) AF: 0.000174 AC: 14 AN: 80502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52574

Middle Eastern (MID) AF: 0.00253 AC: 14 AN: 5526

European-Non Finnish (NFE) AF: 0.0000230 AC: 25 AN: 1086332

Other (OTH) AF: 0.00341 AC: 197 AN: 57732

GnomAD4 genome AF: 0.0151 AC: 2295 AN: 152210 Hom.: 76 Cov.: 32 AF XY: 0.0147 AC XY: 1096 AN XY: 74424

African (AFR) AF: 0.0527 AC: 2186 AN: 41518

American (AMR) AF: 0.00484 AC: 74 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.0680 Hom.: 2807

Bravo AF: 0.0165

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CFAP69-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.83
PhyloP100		1.7
PromoterAI		-0.15	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs17865323; hg19: chr7-89874774;