chr4-185175865-G-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020827.3(CFAP97):​c.1241C>T​(p.Ser414Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CFAP97 NM_020827.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 2 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041861236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP97	NM_020827.3	c.1241C>T	p.Ser414Leu	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>T	p.Ser414Leu	missense_variant	Exon 3 of 5	2	NM_020827.3	ENSP00000409964.2
CFAP97	ENST00000514798.1	c.1241C>T	p.Ser414Leu	missense_variant	Exon 3 of 4	1		ENSP00000423312.1
CFAP97	ENST00000502992.1	n.529C>T		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 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: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 10 AN: 249194 AF XY: 0.0000444

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000389

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461646 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1111818

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

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152050 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 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: 0.000193 AC: 1 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: 0.0000294 AC: 2 AN: 68014

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000331 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1241C>T (p.S414L) alteration is located in exon 3 (coding exon 2) of the CFAP97 gene. This alteration results from a C to T substitution at nucleotide position 1241, causing the serine (S) at amino acid position 414 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;D
REVEL	Benign	0.074
Sift	Benign	0.070	T;D
Sift4G	Benign	0.077	T;D
Polyphen		0.13	B;B
Vest4		0.085
MutPred		0.24		Gain of glycosylation at T410 (P = 0.0122);Gain of glycosylation at T410 (P = 0.0122);
MVP		0.49
MPC		0.019
ClinPred		0.031	T
GERP RS		3.1
Varity_R		0.041
gMVP		0.40
Mutation Taster		=96/4	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; COSMIC: COSV57110755;