chr4-2462871-C-A

Variant names:

• chr4-2462871-C-A
• rs1296411345
• ENST00000635017.1:c.2090C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193282.4(CFAP99):​c.1886C>A​(p.Ala629Glu) variant causes a missense 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. 9/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP99 NM_001193282.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

Genes affected

CFAP99 (HGNC:51180): (cilia and flagella associated protein 99) Predicted to be located in motile cilium. [provided by Alliance of Genome Resources, Apr 2022]

RNF4 (HGNC:10067): (ring finger protein 4) The protein encoded by this gene contains a RING finger motif and acts as a transcription regulator. This protein has been shown to interact with, and inhibit the activity of, TRPS1, a transcription suppressor of GATA-mediated transcription. Transcription repressor ZNF278/PATZ is found to interact with this protein, and thus reduce the enhancement of androgen receptor-dependent transcription mediated by this protein. Studies of the mouse and rat counterparts suggested a role of this protein in spermatogenesis. A pseudogene of this gene is found on chromosome 1.[provided by RefSeq, Jul 2010]

LOC105374353 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13237035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP99	NM_001193282.4	c.1886C>A	p.Ala629Glu	missense_variant	Exon 16 of 16		NP_001180211.2
CFAP99	XM_047415685.1	c.2090C>A	p.Ala697Glu	missense_variant	Exon 15 of 15		XP_047271641.1
LOC105374353	XR_007057992.1	n.-133C>A		upstream_gene_variant
LOC105374353	XR_925057.3	n.-138C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP99	ENST00000635017.1	c.2090C>A	p.Ala697Glu	missense_variant	Exon 15 of 15	5		ENSP00000488922.2
CFAP99	ENST00000506607.2	c.431C>A	p.Ala144Glu	missense_variant	Exon 3 of 3	5
RNF4	ENST00000503659.5	c.-158+266C>A		intron_variant	Intron 1 of 2	4		ENSP00000423186.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1237674 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 608610

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	16
DANN	Benign	0.93
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.46	T;T;T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.97	T
REVEL	Benign	0.033
Sift4G	Pathogenic	0.0	D;T;.
Vest4		0.22
MVP		0.030
ClinPred		0.10	T
GERP RS		0.71
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs1296411345; hg19: chr4-2464598;