5-7885991-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002454.3(MTRR):c.1057+137T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,115,726 control chromosomes in the GnomAD database, including 380,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.84 (53958 hom., cov: 32)
  • Exomes 𝑓: 0.82 (326678 hom.)
• Consequence: MTRR NM_002454.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.771

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-7885991-T-C is Benign according to our data. Variant chr5-7885991-T-C is described in ClinVar as [Benign]. Clinvar id is 1286746.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTRR	NM_002454.3	c.1057+137T>C		intron_variant		ENST00000440940.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTRR	ENST00000440940.7	c.1057+137T>C		intron_variant		1	NM_002454.3	P1

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127784 AN: 152052 Hom.: 53906 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 0.822 AC: 792137 AN: 963554 Hom.: 326678 AF XY: 0.820 AC XY: 408832 AN XY: 498642

Gnomad4 AFR exome AF: 0.890

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.776

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.817

Gnomad4 NFE exome AF: 0.832

Gnomad4 OTH exome AF: 0.821

GnomAD4 genome AF: 0.841 AC: 127902 AN: 152172 Hom.: 53958 Cov.: 32 AF XY: 0.839 AC XY: 62366 AN XY: 74368

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.848

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.818

Gnomad4 NFE AF: 0.829

Gnomad4 OTH AF: 0.825

Alfa AF: 0.832 Hom.: 7682

Bravo AF: 0.842

Asia WGS AF: 0.747 AC: 2600 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.72
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs162037; hg19: chr5-7886104;