7-90245448-G-T

Variant names:

• chr7-90245448-G-T
• rs149099697
• NM_001039706.3:c.24G>T

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_001039706.3(CFAP69):​c.24G>T​(p.Ala8Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,557,814 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (14 hom.)
• Consequence: CFAP69 NM_001039706.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.21
• Publications: 1 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=-0.76).
• BP6: Variant 7-90245448-G-T is Benign according to our data. Variant chr7-90245448-G-T is described in ClinVar as Benign. ClinVar VariationId is 709809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.21 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00665 (1013/152266) while in subpopulation AFR AF = 0.0218 (905/41558). AF 95% confidence interval is 0.0206. There are 10 homozygotes in GnomAd4. There are 472 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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.24G>T	p.Ala8Ala	synonymous	Exon 1 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.24G>T	p.Ala8Ala	synonymous	Exon 1 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.24G>T	p.Ala8Ala	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.24G>T	p.Ala8Ala	synonymous	Exon 1 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.24G>T	p.Ala8Ala	synonymous	Exon 1 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.24G>T	p.Ala8Ala	synonymous	Exon 1 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes AF: 0.00665 AC: 1012 AN: 152148 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00178 AC: 350 AN: 196380 AF XY: 0.00127

Gnomad AFR exome AF: 0.0208

Gnomad AMR exome AF: 0.00271

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000482

Gnomad OTH exome AF: 0.00167

GnomAD4 exome AF: 0.000889 AC: 1250 AN: 1405548 Hom.: 14 Cov.: 31 AF XY: 0.000826 AC XY: 577 AN XY: 698252

African (AFR) AF: 0.0203 AC: 590 AN: 29028

American (AMR) AF: 0.00324 AC: 117 AN: 36096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24038

East Asian (EAS) AF: 0.00 AC: 0 AN: 33258

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80838

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52594

Middle Eastern (MID) AF: 0.00436 AC: 24 AN: 5504

European-Non Finnish (NFE) AF: 0.000342 AC: 372 AN: 1086430

Other (OTH) AF: 0.00251 AC: 145 AN: 57762

GnomAD4 genome AF: 0.00665 AC: 1013 AN: 152266 Hom.: 10 Cov.: 32 AF XY: 0.00634 AC XY: 472 AN XY: 74466

African (AFR) AF: 0.0218 AC: 905 AN: 41558

American (AMR) AF: 0.00379 AC: 58 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68010

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00220 Hom.: 2

Bravo AF: 0.00765

Asia WGS AF: 0.000289 AC: 1 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	-0.76
CADD	Benign	1.2
DANN	Benign	0.69
PhyloP100		-1.2
PromoterAI		-0.021	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: rs149099697; hg19: chr7-89874762;