chr17-9585915-C-T

Variant names:

• chr17-9585915-C-T
• rs143579503
• NM_145054.5:c.213C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_145054.5(CFAP52):​c.213C>T​(p.Ala71Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,613,668 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (7 hom.)
• Consequence: CFAP52 NM_145054.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.179
• Publications: 0 publications found

Genes affected

CFAP52 (HGNC:16053): (cilia and flagella associated protein 52) WD repeat-containing proteins, such as WDR16, play crucial roles in a wide range of physiologic functions, including signal transduction, RNA processing, remodeling the cytoskeleton, regulation of vesicular traffic, and cell division (Silva et al., 2005 [PubMed 15967112]).[supplied by OMIM, Mar 2008]

CFAP52 Gene-Disease associations (from GenCC):

• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• visceral heterotaxy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-9585915-C-T is Benign according to our data. Variant chr17-9585915-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 772897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.179 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145054.5. 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
	CFAP52	NM_145054.5	MANE Select	c.213C>T	p.Ala71Ala	synonymous	Exon 2 of 14	NP_659491.4
	CFAP52	NM_001080556.2		c.71-787C>T		intron	N/A	NP_001074025.1	Q8N1V2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP52	ENST00000352665.10	TSL:1 MANE Select	c.213C>T	p.Ala71Ala	synonymous	Exon 2 of 14	ENSP00000339449.5	Q8N1V2-1
	CFAP52	ENST00000576499.1	TSL:3	c.213C>T	p.Ala71Ala	synonymous	Exon 2 of 4	ENSP00000476293.1	V9GY13
	CFAP52	ENST00000396219.7	TSL:2	c.71-787C>T		intron	N/A	ENSP00000379521.3	Q8N1V2-3

Frequencies

GnomAD3 genomes AF: 0.00172 AC: 261 AN: 151834 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00142

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00206 AC: 519 AN: 251342 AF XY: 0.00199

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000809

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00166

Gnomad NFE exome AF: 0.00379

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00249 AC: 3637 AN: 1461712 Hom.: 7 Cov.: 32 AF XY: 0.00236 AC XY: 1714 AN XY: 727160

African (AFR) AF: 0.000329 AC: 11 AN: 33470

American (AMR) AF: 0.000693 AC: 31 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86254

European-Finnish (FIN) AF: 0.00178 AC: 95 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00301 AC: 3347 AN: 1111878

Other (OTH) AF: 0.00217 AC: 131 AN: 60384

GnomAD4 genome AF: 0.00172 AC: 261 AN: 151956 Hom.: 0 Cov.: 31 AF XY: 0.00164 AC XY: 122 AN XY: 74240

African (AFR) AF: 0.000458 AC: 19 AN: 41472

American (AMR) AF: 0.00105 AC: 16 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5120

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00142 AC: 15 AN: 10536

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

European-Non Finnish (NFE) AF: 0.00302 AC: 205 AN: 67988

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00226 Hom.: 0

Bravo AF: 0.00152

EpiCase AF: 0.00245

EpiControl AF: 0.00308

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Situs inversus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs143579503; hg19: chr17-9489232;