chr18-50266348-T-C

Variant names:

• chr18-50266348-T-C
• rs180778332
• NM_145020.5:c.57A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_145020.5(CFAP53):​c.57A>G​(p.Lys19Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,614,246 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (14 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (123 hom.)
• Consequence: CFAP53 NM_145020.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.695
• Publications: 0 publications found

Genes affected

CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

CFAP53 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 6, autosomal

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 18-50266348-T-C is Benign according to our data. Variant chr18-50266348-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.695 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145020.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	NM_145020.5	MANE Select	c.57A>G	p.Lys19Lys	synonymous	Exon 1 of 8	NP_659457.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	ENST00000398545.5	TSL:1 MANE Select	c.57A>G	p.Lys19Lys	synonymous	Exon 1 of 8	ENSP00000381553.3

Frequencies

GnomAD3 genomes AF: 0.00313 AC: 476 AN: 152258 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.0101 AC: 2520 AN: 249484 AF XY: 0.00735

Gnomad AFR exome AF: 0.000452

Gnomad AMR exome AF: 0.0706

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000334

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.0000795

Gnomad OTH exome AF: 0.00742

GnomAD4 exome AF: 0.00214 AC: 3135 AN: 1461870 Hom.: 123 Cov.: 30 AF XY: 0.00178 AC XY: 1297 AN XY: 727238

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.0650 AC: 2906 AN: 44724

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

East Asian (EAS) AF: 0.00101 AC: 40 AN: 39700

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86258

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111994

Other (OTH) AF: 0.00144 AC: 87 AN: 60394

GnomAD4 genome AF: 0.00314 AC: 478 AN: 152376 Hom.: 14 Cov.: 33 AF XY: 0.00360 AC XY: 268 AN XY: 74524

African (AFR) AF: 0.000433 AC: 18 AN: 41594

American (AMR) AF: 0.0289 AC: 443 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.000393 Hom.: 0

Bravo AF: 0.00649

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Heterotaxy, visceral, 6, autosomal Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		-0.69
PromoterAI		0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs180778332; hg19: chr18-47792718;