chr11-86807686-C-T

Variant names:

• chr11-86807686-C-T
• rs751626725
• NM_007173.6:c.43C>T

Variant summary

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

The NM_007173.6(PRSS23):​c.43C>T​(p.Leu15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRSS23 NM_007173.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

Genes affected

PRSS23 (HGNC:14370): (serine protease 23) This gene encodes a conserved member of the trypsin family of serine proteases. Mouse studies found a decrease of mRNA levels of this gene after ovulation was induced. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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=0.13541552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007173.6. 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
	PRSS23	NM_007173.6	MANE Select	c.43C>T	p.Leu15Phe	missense	Exon 2 of 2	NP_009104.3	O95084-1
	PRSS23	NM_001293179.2		c.43C>T	p.Leu15Phe	missense	Exon 2 of 2	NP_001280108.1	O95084-1
	PRSS23	NM_001293180.2		c.43C>T	p.Leu15Phe	missense	Exon 2 of 2	NP_001280109.1	O95084-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS23	ENST00000280258.6	TSL:1 MANE Select	c.43C>T	p.Leu15Phe	missense	Exon 2 of 2	ENSP00000280258.4	O95084-1
	PRSS23	ENST00000532234.5	TSL:1	n.-12+7035C>T		intron	N/A	ENSP00000436676.1	E9PIB7
	PRSS23	ENST00000893185.1		c.43C>T	p.Leu15Phe	missense	Exon 2 of 2	ENSP00000563244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461688 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727156

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111898

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.063
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	0.098	T
Sift4G	Benign	0.23	T
Polyphen		0.44	B
Vest4		0.10
MutPred		0.24		Loss of helix (P = 0.0626)
MVP		0.39
MPC		0.20
ClinPred		0.30	T
GERP RS		4.9
Varity_R		0.058
gMVP		0.34
Mutation Taster		=78/22	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: rs751626725; hg19: chr11-86518728;