16-58280366-G-C

Variant names:

• chr16-58280366-G-C
• rs750326282
• NM_001305173.2:c.1046C>G

Variant summary

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

The NM_001305173.2(PRSS54):​c.1046C>G​(p.Ala349Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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. A349V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• 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: 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=0.03849742).

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.1046C>G	p.Ala349Gly	missense	Exon 7 of 7	NP_001292102.1	Q6PEW0
	CFAP263	NM_014157.4	MANE Select	c.*589G>C		3_prime_UTR	Exon 9 of 9	NP_054876.2
	PRSS54	NM_001080492.2		c.1046C>G	p.Ala349Gly	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.1046C>G	p.Ala349Gly	missense	Exon 7 of 7	ENSP00000455024.1	Q6PEW0
	CFAP263	ENST00000219299.8	TSL:1 MANE Select	c.*589G>C		3_prime_UTR	Exon 9 of 9	ENSP00000219299.4	Q9H0I3-1
	PRSS54	ENST00000219301.8	TSL:5	c.1046C>G	p.Ala349Gly	missense	Exon 7 of 7	ENSP00000219301.4	Q6PEW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.0050
DANN	Benign	0.48
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.7
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.19
Sift	Benign	0.52	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.20		Gain of disorder (P = 0.0633)
MVP		0.20
MPC		0.14
ClinPred		0.11	T
GERP RS		-12
Varity_R		0.036
gMVP		0.18

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: rs750326282; hg19: chr16-58314270;