rs10038600

Variant names:

• chr5-102902798-G-T
• rs10038600
• NM_001177306.2:c.268+1385G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177306.2(PAM):​c.268+1385G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,198 control chromosomes in the GnomAD database, including 5,699 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 0.26 (5699 hom., cov: 31)
• Consequence: PAM NM_001177306.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAM	NM_001177306.2	c.268+1385G>T		intron_variant	Intron 4 of 25	ENST00000438793.8	NP_001170777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAM	ENST00000438793.8	c.268+1385G>T		intron_variant	Intron 4 of 25	1	NM_001177306.2	ENSP00000396493.3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40024 AN: 151080 Hom.: 5700 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.265 AC: 40021 AN: 151198 Hom.: 5699 Cov.: 31 AF XY: 0.265 AC XY: 19601 AN XY: 73848

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.269

Alfa AF: 0.297 Hom.: 10270

Bravo AF: 0.253

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10038600; hg19: chr5-102238502;