chr16-58280598-C-G

Position:

• chr16-58280598-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001305173.2(PRSS54):​c.814G>C​(p.Gly272Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.956

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]

CCDC113 (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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31715775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.814G>C	p.Gly272Arg	missense_variant	7/7	ENST00000567164.6	NP_001292102.1
CCDC113	NM_014157.4	c.*821C>G		3_prime_UTR_variant	9/9	ENST00000219299.8	NP_054876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6	c.814G>C	p.Gly272Arg	missense_variant	7/7	1	NM_001305173.2	ENSP00000455024.1
CCDC113	ENST00000219299.8	c.*821C>G		3_prime_UTR_variant	9/9	1	NM_014157.4	ENSP00000219299.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

The c.814G>C (p.G272R) alteration is located in exon 7 (coding exon 5) of the PRSS54 gene. This alteration results from a G to C substitution at nucleotide position 814, causing the glycine (G) at amino acid position 272 to be replaced by an arginine (R). 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	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T;T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	.;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;.
Polyphen		1.0	D;D;.;.
Vest4		0.18
MutPred		0.39		Gain of solvent accessibility (P = 0.019);Gain of solvent accessibility (P = 0.019);.;.;
MVP		0.79
MPC		0.51
ClinPred		0.76	D
GERP RS		0.20
Varity_R		0.19
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-58314502;