Variant 12-57768956-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005371.6(METTL1):c.*40T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,581,434 control chromosomes in the GnomAD database, including 103,017 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 0.34 ( 9194 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93823 hom. )

Consequence

METTL1
NM_005371.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

METTL1 (HGNC:7030): (methyltransferase 1, tRNA methylguanosine) This gene is similar in sequence to the S. cerevisiae YDL201w gene. The gene product contains a conserved S-adenosylmethionine-binding motif and is inactivated by phosphorylation. Alternative splice variants encoding different protein isoforms have been described for this gene. A pseudogene has been identified on chromosome X. [provided by RefSeq, Jul 2008]

METTL1 links:

CYP27B1 (HGNC:2606): (cytochrome P450 family 27 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the inner mitochondrial membrane where it hydroxylates 25-hydroxyvitamin D3 at the 1alpha position. This reaction synthesizes 1alpha,25-dihydroxyvitamin D3, the active form of vitamin D3, which binds to the vitamin D receptor and regulates calcium metabolism. Thus this enzyme regulates the level of biologically active vitamin D and plays an important role in calcium homeostasis. Mutations in this gene can result in vitamin D-dependent rickets type I. [provided by RefSeq, Jul 2008]

CYP27B1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
METTL1	NM_005371.6 linkuse as main transcript	c.*40T>C	3_prime_UTR_variant	6/6	ENST00000324871.12	NP_005362.3
METTL1	NM_023033.4 linkuse as main transcript	c.*218T>C	3_prime_UTR_variant	5/5		NP_075422.3
METTL1	XM_005268873.3 linkuse as main transcript	c.*40T>C	3_prime_UTR_variant	7/7		XP_005268930.1
METTL1	XM_047428854.1 linkuse as main transcript	c.*40T>C	3_prime_UTR_variant	5/5		XP_047284810.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
METTL1	ENST00000324871.12 linkuse as main transcript	c.*40T>C	3_prime_UTR_variant	6/6	1	NM_005371.6	ENSP00000314441	P1	Q9UBP6-1
METTL1	ENST00000257848.7 linkuse as main transcript	c.*218T>C	3_prime_UTR_variant	5/5	1		ENSP00000257848		Q9UBP6-2
METTL1	ENST00000547653.1 linkuse as main transcript	c.*218T>C	3_prime_UTR_variant	3/3	3		ENSP00000447838
CYP27B1	ENST00000546609.2 linkuse as main transcript	n.31T>C	non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51388

AN:

151942

Hom.:

9165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.385

Gnomad AMR

AF:

0.285

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.656

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.378

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.288

GnomAD3 exomes

AF:

0.384

AC:

93998

AN:

245090

Hom.:

19687

AF XY:

0.390

AC XY:

51534

AN XY:

132258

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.363

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.634

Gnomad SAS exome

AF:

0.556

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.352

AC:

502796

AN:

1429374

Hom.:

93823

Cov.:

AF XY:

0.357

AC XY:

251672

AN XY:

704614

show subpopulations

Gnomad4 AFR exome

AF:

0.310

Gnomad4 AMR exome

AF:

0.353

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.700

Gnomad4 SAS exome

AF:

0.545

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.327

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.338

AC:

51467

AN:

152060

Hom.:

9194

Cov.:

AF XY:

0.346

AC XY:

25734

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.319

Gnomad4 AMR

AF:

0.285

Gnomad4 ASJ

AF:

0.298

Gnomad4 EAS

AF:

0.656

Gnomad4 SAS

AF:

0.559

Gnomad4 FIN

AF:

0.378

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.326

Hom.:

13758

Bravo

AF:

0.327

Asia WGS

AF:

0.603

AC:

2093

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

9.9

DANN

Benign

0.83

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over