ENST00000635017.1:c.2117G>A

Variant names:

• chr4-2462898-G-A
• rs754618751
• NM_001193282.4:c.1913G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000635017.2(CFAP99):​c.1913G>A​(p.Gly638Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,324,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: CFAP99 ENST00000635017.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.247
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059713572).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635017.2. 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.1913G>A	p.Gly638Glu	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.1913G>A	p.Gly638Glu	missense	Exon 16 of 16	ENSP00000488922.2	D6REC4
	CFAP99	ENST00000860043.1		c.1916G>A	p.Gly639Glu	missense	Exon 16 of 16	ENSP00000530102.1
	RNF4	ENST00000503659.5	TSL:4	c.-158+293G>A		intron	N/A	ENSP00000423186.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 151858 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.000324

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000267 AC: 4 AN: 14996 AF XY: 0.000316

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000637

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000201 AC: 236 AN: 1172394 Hom.: 0 Cov.: 31 AF XY: 0.000198 AC XY: 113 AN XY: 571402

African (AFR) AF: 0.0000427 AC: 1 AN: 23428

American (AMR) AF: 0.00 AC: 0 AN: 10512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16332

East Asian (EAS) AF: 0.00 AC: 0 AN: 26180

South Asian (SAS) AF: 0.00 AC: 0 AN: 43720

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3184

European-Non Finnish (NFE) AF: 0.000236 AC: 230 AN: 975208

Other (OTH) AF: 0.000106 AC: 5 AN: 47204

GnomAD4 genome AF: 0.000158 AC: 24 AN: 151858 Hom.: 0 Cov.: 32 AF XY: 0.000162 AC XY: 12 AN XY: 74190

African (AFR) AF: 0.0000483 AC: 2 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

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

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 67902

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000540 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.0000990 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.93
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.25
REVEL	Benign	0.015
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MVP		0.099
ClinPred		0.023	T
GERP RS		-0.26
gMVP		0.072
Mutation Taster		=99/1	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: rs754618751; hg19: chr4-2464625;