rs2217252

Variant names:

• chr5-102960019-C-A
• rs2217252
• NM_001177306.2:c.1050C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-102960019-C-A
• chr5-102960019-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001177306.2(PAM):​c.1050C>A​(p.Pro350Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P350P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PAM NM_001177306.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844
• Publications: 0 publications found

Genes affected

PAM (HGNC:8596): (peptidylglycine alpha-amidating monooxygenase) This gene encodes a multifunctional protein. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme includes two domains with distinct catalytic activities, a peptidylglycine alpha-hydroxylating monooxygenase (PHM) domain and a peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL) domain. These catalytic domains work sequentially to catalyze the conversion of neuroendocrine peptides to active alpha-amidated products. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.058).
• BP7: Synonymous conserved (PhyloP=-0.844 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177306.2. 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
	PAM	NM_001177306.2	MANE Select	c.1050C>A	p.Pro350Pro	synonymous	Exon 13 of 26	NP_001170777.1	P19021-1
	PAM	NM_001319943.1		c.1050C>A	p.Pro350Pro	synonymous	Exon 13 of 27	NP_001306872.1	O43832
	PAM	NM_000919.4		c.1050C>A	p.Pro350Pro	synonymous	Exon 13 of 26	NP_000910.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAM	ENST00000438793.8	TSL:1 MANE Select	c.1050C>A	p.Pro350Pro	synonymous	Exon 13 of 26	ENSP00000396493.3	P19021-1
	PAM	ENST00000304400.12	TSL:1	c.1050C>A	p.Pro350Pro	synonymous	Exon 13 of 26	ENSP00000306100.8	A0A8C8KD64
	PAM	ENST00000455264.7	TSL:1	c.1050C>A	p.Pro350Pro	synonymous	Exon 13 of 25	ENSP00000403461.2	P19021-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	3.6
DANN	Benign	0.58
PhyloP100		-0.84

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: rs2217252; hg19: chr5-102295723;