NM_001305173.2:c.1051G>A

Variant names:

• chr16-58280361-C-T
• NM_001305173.2:c.1051G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 17/22 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
• 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 -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 VariationId is 2531124.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1051G>A	p.Val351Ile	missense	Exon 7 of 7	NP_001292102.1	Q6PEW0
	CFAP263	NM_014157.4	MANE Select	c.*584C>T		3_prime_UTR	Exon 9 of 9	NP_054876.2
	PRSS54	NM_001080492.2		c.1051G>A	p.Val351Ile	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.1051G>A	p.Val351Ile	missense	Exon 7 of 7	ENSP00000455024.1	Q6PEW0
	CFAP263	ENST00000219299.8	TSL:1 MANE Select	c.*584C>T		3_prime_UTR	Exon 9 of 9	ENSP00000219299.4	Q9H0I3-1
	PRSS54	ENST00000219301.8	TSL:5	c.1051G>A	p.Val351Ile	missense	Exon 7 of 7	ENSP00000219301.4	Q6PEW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	-0.63	N
PhyloP100		-2.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.22
Sift	Benign	0.75	T
Sift4G	Benign	0.70	T
Polyphen		0.0010	B
Vest4		0.016
MutPred		0.20		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

Other links and lift over

hg19: chr16-58314265;