chr1-103573781-A-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001387437.1(AMY2B):c.587A>T(p.Glu196Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,720 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
AMY2B
NM_001387437.1 missense
NM_001387437.1 missense
Scores
4
7
7
Clinical Significance
Conservation
PhyloP100: 1.56
Genes affected
AMY2B (HGNC:478): (amylase alpha 2B) Amylases are secreted proteins that hydrolyze 1,4-alpha-glucoside bonds in oligosaccharides and polysaccharides, and thus catalyze the first step in digestion of dietary starch and glycogen. The human genome has a cluster of several amylase genes that are expressed at high levels in either salivary gland or pancreas. This gene encodes an amylase isoenzyme produced by the pancreas. [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMY2B | NM_001387437.1 | c.587A>T | p.Glu196Val | missense_variant | 4/10 | ENST00000684275.1 | |
AMY2B | NM_001386109.1 | c.587A>T | p.Glu196Val | missense_variant | 6/12 | ||
AMY2B | NM_020978.4 | c.587A>T | p.Glu196Val | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMY2B | ENST00000684275.1 | c.587A>T | p.Glu196Val | missense_variant | 4/10 | NM_001387437.1 | P1 | ||
AMY2B | ENST00000361355.8 | c.587A>T | p.Glu196Val | missense_variant | 6/12 | 1 | P1 | ||
AMY2B | ENST00000491397.1 | n.3856A>T | non_coding_transcript_exon_variant | 4/9 | 5 | ||||
AMY2B | ENST00000477657.5 | c.587A>T | p.Glu196Val | missense_variant, NMD_transcript_variant | 5/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461544Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727088
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2022 | The c.587A>T (p.E196V) alteration is located in exon 6 (coding exon 4) of the AMY2B gene. This alteration results from a A to T substitution at nucleotide position 587, causing the glutamic acid (E) at amino acid position 196 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Pathogenic
D;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;.
REVEL
Uncertain
Sift
Uncertain
D;.
Sift4G
Uncertain
T;T
Polyphen
B;B
Vest4
MutPred
Gain of ubiquitination at K193 (P = 0.0825);Gain of ubiquitination at K193 (P = 0.0825);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at