rs11952361

Variant names:

• chr5-102952216-A-G
• rs11952361
• NM_001177306.2:c.905+1396A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-102952216-A-G
• chr5-102952216-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177306.2(PAM):​c.905+1396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 151,864 control chromosomes in the GnomAD database, including 9,771 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9771 hom., cov: 32)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

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.905+1396A>G		intron	N/A	NP_001170777.1	P19021-1
	PAM	NM_001319943.1		c.905+1396A>G		intron	N/A	NP_001306872.1	O43832
	PAM	NM_000919.4		c.905+1396A>G		intron	N/A	NP_000910.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAM	ENST00000438793.8	TSL:1 MANE Select	c.905+1396A>G		intron	N/A	ENSP00000396493.3	P19021-1
	PAM	ENST00000304400.12	TSL:1	c.905+1396A>G		intron	N/A	ENSP00000306100.8	A0A8C8KD64
	PAM	ENST00000455264.7	TSL:1	c.905+1396A>G		intron	N/A	ENSP00000403461.2	P19021-3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53256 AN: 151746 Hom.: 9753 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.351 AC: 53320 AN: 151864 Hom.: 9771 Cov.: 32 AF XY: 0.347 AC XY: 25775 AN XY: 74216

African (AFR) AF: 0.447 AC: 18493 AN: 41410

American (AMR) AF: 0.272 AC: 4141 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 802 AN: 3464

East Asian (EAS) AF: 0.432 AC: 2230 AN: 5160

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4816

European-Finnish (FIN) AF: 0.336 AC: 3544 AN: 10548

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21959 AN: 67920

Other (OTH) AF: 0.334 AC: 707 AN: 2114

Alfa AF: 0.329 Hom.: 24906

Bravo AF: 0.351

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.33
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs11952361; hg19: chr5-102287920;