4-185175865-G-C

Variant names:

• chr4-185175865-G-C
• rs764958265
• NM_020827.3:c.1241C>G

Variant summary

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

The NM_020827.3(CFAP97):​c.1241C>G​(p.Ser414Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. S414L) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CFAP97 NM_020827.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 2 publications found

Genes affected

CFAP97 (HGNC:29276): (cilia and flagella associated protein 97)

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=0.18940637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP97	NM_020827.3	c.1241C>G	p.Ser414Trp	missense_variant	Exon 3 of 5	ENST00000458385.7	NP_065878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP97	ENST00000458385.7	c.1241C>G	p.Ser414Trp	missense_variant	Exon 3 of 5	2	NM_020827.3	ENSP00000409964.2
CFAP97	ENST00000514798.1	c.1241C>G	p.Ser414Trp	missense_variant	Exon 3 of 4	1		ENSP00000423312.1
CFAP97	ENST00000502992.1	n.529C>G		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152050 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74258

African (AFR) AF: 0.0000242 AC: 1 AN: 41404

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: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.92	T
PhyloP100		1.5
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.058
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.26
MutPred		0.29		Gain of glycosylation at T410 (P = 0.0122);Gain of glycosylation at T410 (P = 0.0122);
MVP		0.56
MPC		0.14
ClinPred		0.79	D
GERP RS		3.1
Varity_R		0.11
gMVP		0.42
Mutation Taster		=95/5	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: rs764958265; hg19: chr4-186097019;