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GeneBe

rs1805087

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1

The NM_000254.3(MTR):c.2756A>G(p.Asp919Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152018 control chromosomes in the gnomAD Genomes database, including 3645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3645 hom., cov: 32)
Exomes 𝑓: 0.20 ( 5663 hom. )

Consequence

MTR
NM_000254.3 missense

Scores

1
5
10

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:5O:1

Conservation

PhyloP100: 8.54

Links

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2
?
Missense variant where missense usually causes diseases, MTR
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0016700923).
BP6
?
Variant 1-236885200-A-G is Benign according to our data. Variant chr1-236885200-A-G is described in ClinVar as [Benign]. Clinvar id is 138289. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-236885200-A-G is described in Lovd as [Benign].
BA1
?
GnomAd highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTRNM_000254.3 linkuse as main transcriptc.2756A>G p.Asp919Gly missense_variant 26/33 ENST00000366577.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTRENST00000366577.10 linkuse as main transcriptc.2756A>G p.Asp919Gly missense_variant 26/331 NM_000254.3 P1Q99707-1

Frequencies

GnomAD3 genomes
AF:
0.213
AC:
32337
AN:
152018
Hom.:
3645
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.263
Gnomad AMI
AF:
0.190
Gnomad AMR
AF:
0.184
Gnomad ASJ
AF:
0.175
Gnomad EAS
AF:
0.122
Gnomad SAS
AF:
0.313
Gnomad FIN
AF:
0.189
Gnomad MID
AF:
0.168
Gnomad NFE
AF:
0.196
Gnomad OTH
AF:
0.188
GnomAD3 exomes
AF:
0.203
AC:
50989
AN:
251124
Hom.:
5663
AF XY:
0.208
AC XY:
28257
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.266
Gnomad AMR exome
AF:
0.184
Gnomad ASJ exome
AF:
0.168
Gnomad EAS exome
AF:
0.111
Gnomad SAS exome
AF:
0.311
Gnomad FIN exome
AF:
0.192
Gnomad NFE exome
AF:
0.191
Gnomad OTH exome
AF:
0.197
GnomAD4 exome
AF:
0.200
AC:
287192
AN:
1438774
Hom.:
30392
AF XY:
0.203
AC XY:
145505
AN XY:
717146
show subpopulations
Gnomad4 AFR exome
AF:
0.268
Gnomad4 AMR exome
AF:
0.182
Gnomad4 ASJ exome
AF:
0.172
Gnomad4 EAS exome
AF:
0.151
Gnomad4 SAS exome
AF:
0.307
Gnomad4 FIN exome
AF:
0.197
Gnomad4 NFE exome
AF:
0.192
Gnomad4 OTH exome
AF:
0.203
Alfa
AF:
0.192
Hom.:
7497
Bravo
AF:
0.209
TwinsUK
AF:
0.203
AC:
752
ALSPAC
AF:
0.199
AC:
768
ESP6500AA
AF:
0.264
AC:
1164
ESP6500EA
AF:
0.198
AC:
1702
ExAC
AF:
0.209
AC:
25325
Asia WGS
AF:
0.218
AC:
758
AN:
3478
EpiCase
AF:
0.182
EpiControl
AF:
0.182

ClinVar

Significance: Benign
Submissions summary: Uncertain:1Benign:5Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Methylcobalamin deficiency type cblG Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Benign, criteria provided, single submitterclinical testingInvitaeNov 01, 2022- -
Gastrointestinal stromal tumor Uncertain:1
Uncertain significance, no assertion criteria providedcase-controlDepartment of Pharmacy and Biotechnology, University of Bologna-- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 09, 2013This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Disorders of Intracellular Cobalamin Metabolism Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaMar 06, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesOct 21, 2022- -
Neural tube defects, folate-sensitive, susceptibility to Other:1
risk factor, no assertion criteria providedliterature onlyOMIMSep 01, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.16
Cadd
Uncertain
24
Dann
Uncertain
0.98
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.76
T;T;T
MetaRNN
Benign
0.0017
T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.00013
P;P
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-4.0
D;D;D
REVEL
Uncertain
0.34
Sift
Benign
0.19
T;T;T
Sift4G
Benign
0.24
T;T;T
Polyphen
0.16
.;B;.
Vest4
0.22
MPC
0.70
ClinPred
0.040
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.29
gMVP
0.58

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

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

Other links and lift over

dbSNP: rs1805087; hg19: chr1-237048500; COSMIC: COSV63964936; API