6-150899109-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015440.5(MTHFD1L):c.781-6541A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 448,792 control chromosomes in the GnomAD database, including 65,886 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 0.56 (24021 hom., cov: 32)
  • Exomes 𝑓: 0.52 (41865 hom.)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.781-6541A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.781-6541A>G		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84457 AN: 151918 Hom.: 23996 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.522 AC: 154911 AN: 296756 Hom.: 41865 AF XY: 0.522 AC XY: 73999 AN XY: 141764

Gnomad4 AFR exome AF: 0.522

Gnomad4 AMR exome AF: 0.631

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.802

Gnomad4 SAS exome AF: 0.708

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.556 AC: 84528 AN: 152036 Hom.: 24021 Cov.: 32 AF XY: 0.567 AC XY: 42158 AN XY: 74314

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.562

Alfa AF: 0.534 Hom.: 2768

Bravo AF: 0.553

Asia WGS AF: 0.728 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.58
Dann	Benign	0.80

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: rs803419; hg19: chr6-151220245;