rs12199063

Variant names:

• chr6-151086000-G-A
• rs12199063
• NM_015440.5:c.2848-6467G>A

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2848-6467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,786 control chromosomes in the GnomAD database, including 7,309 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 0.30 (7309 hom., cov: 30)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170
• Publications: 2 publications found

Genes affected

MTHFD1L (HGNC:21055): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like) The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2848-6467G>A		intron_variant	Intron 26 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2848-6467G>A		intron_variant	Intron 26 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2851-6467G>A		intron_variant	Intron 26 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.2653-6467G>A		intron_variant	Intron 26 of 27	5		ENSP00000479539.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45878 AN: 151668 Hom.: 7301 Cov.: 30

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.302 AC: 45908 AN: 151786 Hom.: 7309 Cov.: 30 AF XY: 0.309 AC XY: 22885 AN XY: 74142

African (AFR) AF: 0.227 AC: 9411 AN: 41378

American (AMR) AF: 0.289 AC: 4404 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1097 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1453 AN: 5150

South Asian (SAS) AF: 0.469 AC: 2247 AN: 4786

European-Finnish (FIN) AF: 0.380 AC: 3997 AN: 10516

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22373 AN: 67916

Other (OTH) AF: 0.322 AC: 678 AN: 2104

Alfa AF: 0.311 Hom.: 1548

Bravo AF: 0.285

Asia WGS AF: 0.374 AC: 1299 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.68
PhyloP100		0.017
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

Other links and lift over

dbSNP: rs12199063; hg19: chr6-151407136;