16-58280459-C-T

Variant names:

• chr16-58280459-C-T
• rs767013153
• NM_001305173.2:c.953G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001305173.2(PRSS54):​c.953G>A​(p.Arg318Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. R318T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038885772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.953G>A	p.Arg318Lys	missense_variant	Exon 7 of 7	ENST00000567164.6	NP_001292102.1
CFAP263	NM_014157.4	c.*682C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000219299.8	NP_054876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRSS54	ENST00000567164.6	c.953G>A	p.Arg318Lys	missense_variant	Exon 7 of 7	1	NM_001305173.2	ENSP00000455024.1
CCDC113	ENST00000219299.8	c.*682C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_014157.4	ENSP00000219299.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 249008 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134788

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.15
DANN	Benign	0.55
DEOGEN2	Benign	0.00053	T;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.30	.;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.010	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.85	T;T;T
Sift4G	Benign	0.91	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.044
MutPred		0.23		Gain of methylation at R318 (P = 0.0129);Gain of methylation at R318 (P = 0.0129);.;
MVP		0.43
MPC		0.14
ClinPred		0.018	T
GERP RS		-3.5
Varity_R		0.042
gMVP		0.24

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

LitVar

Other links and lift over

dbSNP: rs767013153; hg19: chr16-58314363;