chr16-58280715-C-G

Variant names:

• chr16-58280715-C-G
• rs769699261
• NM_001305173.2:c.697G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001305173.2(PRSS54):​c.697G>C​(p.Asp233His) 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 1,461,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. D233N) has been classified as Likely benign.

• 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: -0.0240
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24506864).

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.697G>C	p.Asp233His	missense	Exon 7 of 7	NP_001292102.1	Q6PEW0
	CFAP263	NM_014157.4	MANE Select	c.*938C>G		3_prime_UTR	Exon 9 of 9	NP_054876.2
	PRSS54	NM_001080492.2		c.697G>C	p.Asp233His	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.697G>C	p.Asp233His	missense	Exon 7 of 7	ENSP00000455024.1	Q6PEW0
	CFAP263	ENST00000219299.8	TSL:1 MANE Select	c.*938C>G		3_prime_UTR	Exon 9 of 9	ENSP00000219299.4	Q9H0I3-1
	PRSS54	ENST00000219301.8	TSL:5	c.697G>C	p.Asp233His	missense	Exon 7 of 7	ENSP00000219301.4	Q6PEW0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461206 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726778

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111462

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.024
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.15
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.052	T
Polyphen		0.99	D
Vest4		0.20
MutPred		0.51		Loss of stability (P = 0.1918)
MVP		0.72
MPC		0.67
ClinPred		0.57	D
GERP RS		-0.36
Varity_R		0.082
gMVP		0.63
Mutation Taster		=97/3	polymorphism

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

dbSNP: rs769699261; hg19: chr16-58314619;