rs936340179

Variant names:

• chr4-2462544-G-A
• rs936340179
• NM_001193282.4:c.1763G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-2462544-G-A
• chr4-2462544-G-C

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.1763G>A​(p.Arg588His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00006 in 1,466,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: CFAP99 NM_001193282.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88
• 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]

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=0.17642808).

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.1763G>A	p.Arg588His	missense	Exon 15 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.1763G>A	p.Arg588His	missense	Exon 15 of 16	ENSP00000488922.2	D6REC4
	CFAP99	ENST00000860043.1		c.1766G>A	p.Arg589His	missense	Exon 15 of 16	ENSP00000530102.1
	RNF4	ENST00000503659.5	TSL:4	c.-219G>A		5_prime_UTR	Exon 1 of 3	ENSP00000423186.1

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152012 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: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000819 AC: 6 AN: 73262 AF XY: 0.0000942

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000143

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000112

Gnomad OTH exome AF: 0.000466

GnomAD4 exome AF: 0.0000624 AC: 82 AN: 1314566 Hom.: 0 Cov.: 33 AF XY: 0.0000695 AC XY: 45 AN XY: 647646

African (AFR) AF: 0.00 AC: 0 AN: 26470

American (AMR) AF: 0.000118 AC: 3 AN: 25380

Ashkenazi Jewish (ASJ) AF: 0.0000435 AC: 1 AN: 23010

East Asian (EAS) AF: 0.00 AC: 0 AN: 28060

South Asian (SAS) AF: 0.00 AC: 0 AN: 72090

European-Finnish (FIN) AF: 0.0000916 AC: 3 AN: 32736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3902

European-Non Finnish (NFE) AF: 0.0000706 AC: 74 AN: 1048424

Other (OTH) AF: 0.0000184 AC: 1 AN: 54494

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152012 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74250

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

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

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10580

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67968

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

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	0.26
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	27
DANN	Pathogenic	1.0
Eigen	Benign	0.12
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.34	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.68	T
PhyloP100		1.9
REVEL	Benign	0.18
Sift4G	Uncertain	0.029	D
Vest4		0.45
MVP		0.072
ClinPred		0.51	D
GERP RS		3.4
PromoterAI		-0.012	Neutral
gMVP		0.23
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: rs936340179; hg19: chr4-2464271;