5-102949581-C-T

Variant names:

• chr5-102949581-C-T
• NM_001177306.2:c.688C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001177306.2(PAM):​c.688C>T​(p.His230Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,394,786 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PAM NM_001177306.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.96

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3177563).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAM	NM_001177306.2	c.688C>T	p.His230Tyr	missense_variant	Exon 10 of 26	ENST00000438793.8	NP_001170777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAM	ENST00000438793.8	c.688C>T	p.His230Tyr	missense_variant	Exon 10 of 26	1	NM_001177306.2	ENSP00000396493.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1394786 Hom.: 0 Cov.: 23 AF XY: 0.00000143 AC XY: 1 AN XY: 697654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;.;.;.;.
Eigen	Benign	0.090
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.80	N;N;N;N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.42	T;T;T;T;T
Polyphen		0.37	B;B;B;B;B
Vest4		0.42
MutPred		0.76		Gain of methylation at K225 (P = 0.0505);Gain of methylation at K225 (P = 0.0505);Gain of methylation at K225 (P = 0.0505);Gain of methylation at K225 (P = 0.0505);Gain of methylation at K225 (P = 0.0505);
MVP		0.59
MPC		0.66
ClinPred		0.71	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-102285285;