chr7-90258161-C-T

Variant names:

• chr7-90258161-C-T
• NM_001039706.3:c.244C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001039706.3(CFAP69):​c.244C>T​(p.Leu82Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CFAP69 NM_001039706.3 missense, splice_region
• Scores: Splicing: ADA: 0.003347
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.746
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050317615).
• BP6: Variant 7-90258161-C-T is Benign according to our data. Variant chr7-90258161-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2283741.Status of the report is criteria_provided_single_submitter, 1 stars.

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.244C>T	p.Leu82Phe	missense splice_region	Exon 3 of 23	NP_001034795.2	A5D8W1-1
	CFAP69	NM_001160138.2		c.244C>T	p.Leu82Phe	missense splice_region	Exon 3 of 23	NP_001153610.1	A5D8W1-5
	CFAP69	NM_001363438.1		c.244C>T	p.Leu82Phe	missense splice_region	Exon 3 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.244C>T	p.Leu82Phe	missense splice_region	Exon 3 of 23	ENSP00000373948.4	A5D8W1-1
	CFAP69	ENST00000497910.5	TSL:2	c.244C>T	p.Leu82Phe	missense splice_region	Exon 3 of 23	ENSP00000419549.1	A5D8W1-5
	CFAP69	ENST00000949775.1		c.244C>T	p.Leu82Phe	missense splice_region	Exon 3 of 22	ENSP00000619834.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.4
DANN	Benign	0.44
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.75
PROVEAN	Benign	1.3	N
REVEL	Benign	0.082
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.64		Gain of catalytic residue at C77 (P = 0.1468)
MVP		0.055
MPC		0.069
ClinPred		0.041	T
GERP RS		-3.5
PromoterAI		0.0010	Neutral
Varity_R		0.040
gMVP		0.13
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0033
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

hg19: chr7-89887475;