6-150894458-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.780+6477A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,042 control chromosomes in the GnomAD database, including 48,386 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 0.79 (48386 hom., cov: 30)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.780+6477A>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.780+6477A>G		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120170 AN: 151924 Hom.: 48330 Cov.: 30

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.791 AC: 120287 AN: 152042 Hom.: 48386 Cov.: 30 AF XY: 0.798 AC XY: 59314 AN XY: 74288

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.816

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.788

Alfa AF: 0.710 Hom.: 59417

Bravo AF: 0.795

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	3.8
Dann	Benign	0.75

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: rs803422; hg19: chr6-151215594; COSMIC: COSV66208291;