16-58280282-T-A

Position:

• chr16-58280282-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001305173.2(PRSS54):​c.1130A>T​(p.Gln377Leu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PRSS54 NM_001305173.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16198647).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRSS54	NM_001305173.2	c.1130A>T	p.Gln377Leu	missense_variant	7/7	ENST00000567164.6	NP_001292102.1
CCDC113	NM_014157.4	c.*505T>A		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.1130A>T	p.Gln377Leu	missense_variant	7/7	1	NM_001305173.2	ENSP00000455024.1
CCDC113	ENST00000219299.8	c.*505T>A		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: 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

Mar 02, 2023

The c.1130A>T (p.Q377L) alteration is located in exon 7 (coding exon 5) of the PRSS54 gene. This alteration results from a A to T substitution at nucleotide position 1130, causing the glutamine (Q) at amino acid position 377 to be replaced by a leucine (L). 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	Benign	0.12
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.011	T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.58	.;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.55
Sift	Benign	0.34	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.82	P;P;.
Vest4		0.16
MutPred		0.48		Gain of catalytic residue at Q377 (P = 0.0071);Gain of catalytic residue at Q377 (P = 0.0071);.;
MVP		0.73
MPC		0.51
ClinPred		0.23	T
GERP RS		-0.62
Varity_R		0.069
gMVP		0.52

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: chr16-58314186;