4-7041953-C-G

Variant names:

• chr4-7041953-C-G
• rs776600923
• NM_153376.3:c.986G>C

Variant summary

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

The NM_153376.3(CFAP184):​c.986G>C​(p.Arg329Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R329H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CFAP184 NM_153376.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

CFAP184 (HGNC:26900): (cilia and flagella associated protein 184) Predicted to be involved in cilium assembly. Predicted to be active in axoneme and ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

TADA2B (HGNC:30781): (transcriptional adaptor 2B) TADA2B functions as a transcriptional adaptor protein that potentiates transcription through coordination of histone acetyltransferase (HAT) activity and by linking activation factors to basal transcriptional machinery (Barlev et al., 2003 [PubMed 12972612]).[supplied by OMIM, Apr 2010]

ENSG00000245748 (HGNC:58725):

LOC100129931 (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=0.1464228).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153376.3. 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
	CFAP184	NM_153376.3	MANE Select	c.986G>C	p.Arg329Pro	missense	Exon 1 of 1	NP_699207.1	Q2M329
	LOC100129931	NR_033828.1		n.696+3027G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP184	ENST00000310085.6	TSL:6 MANE Select	c.986G>C	p.Arg329Pro	missense	Exon 1 of 1	ENSP00000309285.4	Q2M329
	TADA2B	ENST00000506692.1	TSL:2	c.-140C>G		5_prime_UTR	Exon 1 of 2	ENSP00000422398.1	D6RC20
	ENSG00000245748	ENST00000500031.1	TSL:2	n.696+3027G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460282 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726424

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111880

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.068
Sift	Benign	0.069	T
Sift4G	Benign	0.27	T
Polyphen		0.98	D
Vest4		0.29
MutPred		0.33		Loss of stability (P = 0.1097)
MVP		0.22
ClinPred		0.76	D
GERP RS		0.077
PromoterAI		-0.011	Neutral
Varity_R		0.41
gMVP		0.83
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: rs776600923; hg19: chr4-7043680;