rs326122

Variant names:

• chr5-7876498-G-A
• rs326122
• NM_002454.3:c.401+1123G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-7876498-G-A
• chr5-7876498-G-C
• chr5-7876498-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002454.3(MTRR):​c.401+1123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 152,266 control chromosomes in the GnomAD database, including 56,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56415 hom., cov: 33)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 9 publications found

Genes affected

MTRR (HGNC:7473): (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) This gene encodes a member of the ferredoxin-NADP(+) reductase (FNR) family of electron transferases. This protein functions in the synthesis of methionine by regenerating methionine synthase to a functional state. Because methionine synthesis requires methyl-group transfer by a folate donor, activity of the encoded enzyme is important for folate metabolism and cellular methylation. Mutations in this gene can cause homocystinuria-megaloblastic anemia, cbl E type. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MTRR Gene-Disease associations (from GenCC):

• methylcobalamin deficiency type cblE

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTRR	NM_002454.3	c.401+1123G>A		intron_variant	Intron 4 of 14	ENST00000440940.7	NP_002445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTRR	ENST00000440940.7	c.401+1123G>A		intron_variant	Intron 4 of 14	1	NM_002454.3	ENSP00000402510.2

Frequencies

GnomAD3 genomes AF: 0.859 AC: 130683 AN: 152148 Hom.: 56359 Cov.: 33

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.847

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.859 AC: 130803 AN: 152266 Hom.: 56415 Cov.: 33 AF XY: 0.856 AC XY: 63758 AN XY: 74446

African (AFR) AF: 0.912 AC: 37901 AN: 41564

American (AMR) AF: 0.862 AC: 13193 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2778 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3467 AN: 5170

South Asian (SAS) AF: 0.809 AC: 3904 AN: 4828

European-Finnish (FIN) AF: 0.842 AC: 8919 AN: 10594

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.850 AC: 57838 AN: 68014

Other (OTH) AF: 0.845 AC: 1786 AN: 2114

Alfa AF: 0.851 Hom.: 9592

Bravo AF: 0.860

Asia WGS AF: 0.750 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.22
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs326122; hg19: chr5-7876611;