rs12199063

Positions:

• chr6-151086000-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

MTHFD1L (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2848-6467G>A		intron_variant		ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2848-6467G>A		intron_variant		1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2851-6467G>A		intron_variant		5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.2653-6467G>A		intron_variant		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

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.322

Alfa AF: 0.313 Hom.: 1528

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

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

Other links and lift over

dbSNP: rs12199063; hg19: chr6-151407136;