chr16-58280361-C-T

Position:

• chr16-58280361-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001305173.2(PRSS54):​c.1051G>A​(p.Val351Ile) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.31

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037157148).
• BP6: Variant 16-58280361-C-T is Benign according to our data. Variant chr16-58280361-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2531124.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.1051G>A	p.Val351Ile	missense_variant	7/7	ENST00000567164.6	NP_001292102.1
CCDC113	NM_014157.4	c.*584C>T		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.1051G>A	p.Val351Ile	missense_variant	7/7	1	NM_001305173.2	ENSP00000455024.1
CCDC113	ENST00000219299.8	c.*584C>T		3_prime_UTR_variant	9/9	1	NM_014157.4	ENSP00000219299.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.0010
DANN	Benign	0.57
DEOGEN2	Benign	0.00026	T;T;.
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.29	.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.037	T;T;T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.63	N;N;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.70	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.016
MutPred		0.20		Gain of catalytic residue at P353 (P = 0.0307);Gain of catalytic residue at P353 (P = 0.0307);.;
MVP		0.40
MPC		0.11
ClinPred		0.050	T
GERP RS		-11
Varity_R		0.020
gMVP		0.10

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: chr16-58314265;