chr1-236885376-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000254.3(MTR):​c.2775+157G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,086 control chromosomes in the GnomAD database, including 7,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 7550 hom., cov: 32)

Consequence

MTR
NM_000254.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.749

Publications

45 publications found
Variant links:
Genes affected
MTR (HGNC:7468): (5-methyltetrahydrofolate-homocysteine methyltransferase) This gene encodes the 5-methyltetrahydrofolate-homocysteine methyltransferase. This enzyme, also known as cobalamin-dependent methionine synthase, catalyzes the final step in methionine biosynthesis. Mutations in MTR have been identified as the underlying cause of methylcobalamin deficiency complementation group G. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]
MTR Gene-Disease associations (from GenCC):
  • methylcobalamin deficiency type cblG
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 1-236885376-G-T is Benign according to our data. Variant chr1-236885376-G-T is described in ClinVar as Benign. ClinVar VariationId is 1282022.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTRNM_000254.3 linkc.2775+157G>T intron_variant Intron 26 of 32 ENST00000366577.10 NP_000245.2 Q99707-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTRENST00000366577.10 linkc.2775+157G>T intron_variant Intron 26 of 32 1 NM_000254.3 ENSP00000355536.5 Q99707-1
MTRENST00000366576.3 linkc.1437+157G>T intron_variant Intron 13 of 19 1 ENSP00000355535.3 B1ANE3

Frequencies

GnomAD3 genomes
AF:
0.290
AC:
44135
AN:
151968
Hom.:
7532
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.468
Gnomad AMI
AF:
0.224
Gnomad AMR
AF:
0.231
Gnomad ASJ
AF:
0.184
Gnomad EAS
AF:
0.174
Gnomad SAS
AF:
0.407
Gnomad FIN
AF:
0.206
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.217
Gnomad OTH
AF:
0.261
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.291
AC:
44195
AN:
152086
Hom.:
7550
Cov.:
32
AF XY:
0.291
AC XY:
21673
AN XY:
74358
show subpopulations
African (AFR)
AF:
0.468
AC:
19393
AN:
41440
American (AMR)
AF:
0.231
AC:
3535
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.184
AC:
637
AN:
3466
East Asian (EAS)
AF:
0.174
AC:
899
AN:
5170
South Asian (SAS)
AF:
0.405
AC:
1954
AN:
4820
European-Finnish (FIN)
AF:
0.206
AC:
2177
AN:
10580
Middle Eastern (MID)
AF:
0.218
AC:
64
AN:
294
European-Non Finnish (NFE)
AF:
0.217
AC:
14766
AN:
67998
Other (OTH)
AF:
0.268
AC:
566
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1522
3044
4566
6088
7610
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
434
868
1302
1736
2170
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.241
Hom.:
13038
Bravo
AF:
0.295
Asia WGS
AF:
0.304
AC:
1058
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 01, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
5.9
DANN
Benign
0.70
PhyloP100
-0.75
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs2275565; hg19: chr1-237048676; API