2-232521331-C-T

Variant names:

• chr2-232521331-C-T
• NM_001195129.2:c.108C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001195129.2(PRSS56):​c.108C>T​(p.Ala36Ala) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PRSS56 NM_001195129.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0400
• Publications: 0 publications found

Genes affected

PRSS56 (HGNC:39433): (serine protease 56) This gene encodes a protein that contains a peptidase S1 domain and possesses trypsin-like serine protease activity. The encoded protein may play a role in eye development, and mutations in this gene are a cause of autosomal recessive posterior microphthalmos. [provided by RefSeq, Dec 2011]

PRSS56 Gene-Disease associations (from GenCC):

• isolated microphthalmia 6

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nanophthalmia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 2-232521331-C-T is Benign according to our data. Variant chr2-232521331-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2759910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.04 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195129.2. 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
	PRSS56	NM_001195129.2	MANE Select	c.108C>T	p.Ala36Ala	synonymous	Exon 2 of 13	NP_001182058.1	P0CW18
	PRSS56	NM_001369848.1		c.108C>T	p.Ala36Ala	synonymous	Exon 2 of 13	NP_001356777.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRSS56	ENST00000617714.2	TSL:5 MANE Select	c.108C>T	p.Ala36Ala	synonymous	Exon 2 of 13	ENSP00000479745.1	P0CW18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Isolated microphthalmia 6 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.7
DANN	Benign	0.86
PhyloP100		0.040
Mutation Taster		=100/0	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

hg19: chr2-233386041;