chr10-113567499-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004132.5(HABP2):ā€‹c.80T>Gā€‹(p.Met27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,460,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.000016 ( 0 hom. )

Consequence

HABP2
NM_004132.5 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0860
Variant links:
Genes affected
HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.19532031).
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
HABP2NM_004132.5 linkuse as main transcriptc.80T>G p.Met27Arg missense_variant 2/13 ENST00000351270.4 NP_004123.1
HABP2NM_001177660.3 linkuse as main transcriptc.2T>G p.Met1? start_lost 2/13 NP_001171131.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HABP2ENST00000351270.4 linkuse as main transcriptc.80T>G p.Met27Arg missense_variant 2/131 NM_004132.5 ENSP00000277903 P1Q14520-1
HABP2ENST00000542051.5 linkuse as main transcriptc.2T>G p.Met1? start_lost 2/132 ENSP00000443283 Q14520-2
HABP2ENST00000460714.1 linkuse as main transcriptn.16T>G non_coding_transcript_exon_variant 1/23

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251374
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1460222
Hom.:
0
Cov.:
30
AF XY:
0.0000151
AC XY:
11
AN XY:
726584
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

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 GeneticsAug 02, 2022The c.80T>G (p.M27R) alteration is located in exon 2 (coding exon 2) of the HABP2 gene. This alteration results from a T to G substitution at nucleotide position 80, causing the methionine (M) at amino acid position 27 to be replaced by an arginine (R). 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
Benign
0.086
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
7.7
DANN
Benign
0.78
DEOGEN2
Benign
0.036
.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.022
N
LIST_S2
Uncertain
0.90
D;T
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
1.8
.;L
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.6
N;N
REVEL
Uncertain
0.29
Sift
Uncertain
0.0030
D;T
Sift4G
Uncertain
0.0090
D;T
Polyphen
0.021
.;B
Vest4
0.52
MutPred
0.30
.;Gain of loop (P = 0.1069);
MVP
0.29
MPC
0.0090
ClinPred
0.14
T
GERP RS
-1.1
Varity_R
0.26
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
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: rs745740374; hg19: chr10-115327258; API