rs1964703629

Variant names:

• chr16-58280751-G-C
• rs1964703629
• NM_001305173.2:c.661C>G

Variant summary

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

The NM_001305173.2(PRSS54):​c.661C>G​(p.Pro221Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,448,054 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.17
• Publications: 0 publications found

Genes affected

PRSS54 (HGNC:26336): (serine protease 54) This gene encodes a putative serine-type endopeptidase containing the peptidase S1 domain. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]

CFAP263 (HGNC:25002): (cilia and flagella associated protein 263) Involved in cilium assembly. Located in centriolar satellite and ciliary basal body. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305173.2. 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
	PRSS54	NM_001305173.2	MANE Select	c.661C>G	p.Pro221Ala	missense	Exon 7 of 7	NP_001292102.1	Q6PEW0
	CFAP263	NM_014157.4	MANE Select	c.*974G>C		3_prime_UTR	Exon 9 of 9	NP_054876.2
	PRSS54	NM_001080492.2		c.661C>G	p.Pro221Ala	missense	Exon 7 of 7	NP_001073961.1	Q6PEW0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS54	ENST00000567164.6	TSL:1 MANE Select	c.661C>G	p.Pro221Ala	missense	Exon 7 of 7	ENSP00000455024.1	Q6PEW0
	CFAP263	ENST00000219299.8	TSL:1 MANE Select	c.*974G>C		3_prime_UTR	Exon 9 of 9	ENSP00000219299.4	Q9H0I3-1
	PRSS54	ENST00000219301.8	TSL:5	c.661C>G	p.Pro221Ala	missense	Exon 7 of 7	ENSP00000219301.4	Q6PEW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000829 AC: 12 AN: 1448054 Hom.: 0 Cov.: 32 AF XY: 0.00000836 AC XY: 6 AN XY: 717930

African (AFR) AF: 0.00 AC: 0 AN: 33096

American (AMR) AF: 0.00 AC: 0 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25626

East Asian (EAS) AF: 0.00 AC: 0 AN: 39400

South Asian (SAS) AF: 0.00 AC: 0 AN: 85484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1102268

Other (OTH) AF: 0.00 AC: 0 AN: 59682

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	1.6	L
PhyloP100		1.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.61
Sift	Uncertain	0.026	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.61		Loss of glycosylation at P221 (P = 0.0751)
MVP		0.85
MPC		0.44
ClinPred		0.81	D
GERP RS		3.8
Varity_R		0.27
gMVP		0.66
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1964703629; hg19: chr16-58314655;