NM_015440.5:c.780+6477A>G

Variant names:

• chr6-150894458-A-G
• rs803422
• NM_015440.5:c.780+6477A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.780+6477A>G		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.783+6477A>G		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.585+6477A>G		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.780+6477A>G		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000367307.8	TSL:1	c.781-4402A>G		intron	N/A	ENSP00000356276.4	Q6UB35-2
	MTHFD1L	ENST00000611279.4	TSL:5	c.783+6477A>G		intron	N/A	ENSP00000478253.1	B7ZM99

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

African (AFR) AF: 0.907 AC: 37629 AN: 41486

American (AMR) AF: 0.816 AC: 12462 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2585 AN: 3466

East Asian (EAS) AF: 0.998 AC: 5171 AN: 5180

South Asian (SAS) AF: 0.870 AC: 4180 AN: 4802

European-Finnish (FIN) AF: 0.778 AC: 8224 AN: 10564

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47491 AN: 67950

Other (OTH) AF: 0.788 AC: 1662 AN: 2110

Alfa AF: 0.731 Hom.: 103197

Bravo AF: 0.795

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		0.18
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: rs803422; hg19: chr6-151215594; COSMIC: COSV66208291;