chr4-2462871-C-T

Variant names:

• chr4-2462871-C-T
• rs1296411345
• NM_001193282.4:c.1886C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001193282.4(CFAP99):​c.1886C>T​(p.Ala629Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,389,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CFAP99 NM_001193282.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.270
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12747556).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001193282.4. 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
	CFAP99	NM_001193282.4	MANE Select	c.1886C>T	p.Ala629Val	missense	Exon 16 of 16	NP_001180211.2	D6REC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP99	ENST00000635017.2	TSL:5 MANE Select	c.1886C>T	p.Ala629Val	missense	Exon 16 of 16	ENSP00000488922.2	D6REC4
	CFAP99	ENST00000860043.1		c.1889C>T	p.Ala630Val	missense	Exon 16 of 16	ENSP00000530102.1
	RNF4	ENST00000503659.5	TSL:4	c.-158+266C>T		intron	N/A	ENSP00000423186.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151780 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000162 AC: 2 AN: 1237674 Hom.: 0 Cov.: 31 AF XY: 0.00000329 AC XY: 2 AN XY: 608610

African (AFR) AF: 0.00 AC: 0 AN: 24964

American (AMR) AF: 0.00 AC: 0 AN: 19476

Ashkenazi Jewish (ASJ) AF: 0.0000499 AC: 1 AN: 20046

East Asian (EAS) AF: 0.00 AC: 0 AN: 26372

South Asian (SAS) AF: 0.00 AC: 0 AN: 59898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3512

European-Non Finnish (NFE) AF: 9.96e-7 AC: 1 AN: 1003582

Other (OTH) AF: 0.00 AC: 0 AN: 50110

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151780 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74142

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.00 AC: 0 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67896

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.17
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	15
DANN	Uncertain	0.98
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.50	T
M_CAP	Pathogenic	0.38	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.27
REVEL	Benign	0.035
Sift4G	Pathogenic	0.0	D
Vest4		0.18
MVP		0.030
ClinPred		0.088	T
GERP RS		0.71
gMVP		0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1296411345; hg19: chr4-2464598;