9-114061098-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001633.4(AMBP):​c.854C>T​(p.Ala285Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000149 in 1,613,774 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

AMBP
NM_001633.4 missense, splice_region

Scores

9
10
Splicing: ADA: 0.3393
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29
Variant links:
Genes affected
AMBP (HGNC:453): (alpha-1-microglobulin/bikunin precursor) This gene encodes a complex glycoprotein secreted in plasma. The precursor is proteolytically processed into distinct functioning proteins: alpha-1-microglobulin, which belongs to the superfamily of lipocalin transport proteins and may play a role in the regulation of inflammatory processes, and bikunin, which is a urinary trypsin inhibitor belonging to the superfamily of Kunitz-type protease inhibitors and plays an important role in many physiological and pathological processes. This gene is located on chromosome 9 in a cluster of lipocalin genes. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22736275).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AMBPNM_001633.4 linkuse as main transcriptc.854C>T p.Ala285Val missense_variant, splice_region_variant 9/10 ENST00000265132.8 NP_001624.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AMBPENST00000265132.8 linkuse as main transcriptc.854C>T p.Ala285Val missense_variant, splice_region_variant 9/101 NM_001633.4 ENSP00000265132 P1
AMBPENST00000466610.6 linkuse as main transcriptc.494-21C>T intron_variant 3 ENSP00000475149
AMBPENST00000540645.5 linkuse as main transcriptn.1168C>T non_coding_transcript_exon_variant 8/82

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000840
AC:
21
AN:
249872
Hom.:
0
AF XY:
0.0000888
AC XY:
12
AN XY:
135120
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000871
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461416
Hom.:
1
Cov.:
31
AF XY:
0.0000179
AC XY:
13
AN XY:
726976
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000353
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152358
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 submitterclinical testingAmbry GeneticsJul 19, 2023The c.854C>T (p.A285V) alteration is located in exon 9 (coding exon 9) of the AMBP gene. This alteration results from a C to T substitution at nucleotide position 854, causing the alanine (A) at amino acid position 285 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.31
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.7
D
REVEL
Benign
0.20
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.018
D
Polyphen
1.0
D
Vest4
0.54
MutPred
0.58
Loss of catalytic residue at A285 (P = 0.1459);
MVP
0.68
MPC
0.30
ClinPred
0.32
T
GERP RS
4.1
Varity_R
0.53
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.34
dbscSNV1_RF
Benign
0.34
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs530034584; hg19: chr9-116823378; COSMIC: COSV105019617; COSMIC: COSV105019617; API