6-150876595-A-G

Variant names:

• chr6-150876595-A-G
• rs2073066
• NM_015440.5:c.312+421A>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.312+421A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,216 control chromosomes in the GnomAD database, including 2,281 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 0.17 (2281 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.18
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.312+421A>G		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.312+421A>G		intron	N/A	NP_001229696.1
	MTHFD1L	NM_001242768.2		c.114+421A>G		intron	N/A	NP_001229697.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.312+421A>G		intron	N/A	ENSP00000356290.3
	MTHFD1L	ENST00000367307.8	TSL:1	c.312+421A>G		intron	N/A	ENSP00000356276.4
	MTHFD1L	ENST00000611279.4	TSL:5	c.312+421A>G		intron	N/A	ENSP00000478253.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25365 AN: 152098 Hom.: 2284 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.167 AC: 25364 AN: 152216 Hom.: 2281 Cov.: 32 AF XY: 0.170 AC XY: 12620 AN XY: 74416

African (AFR) AF: 0.114 AC: 4723 AN: 41544

American (AMR) AF: 0.120 AC: 1837 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 665 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5176

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4822

European-Finnish (FIN) AF: 0.242 AC: 2566 AN: 10586

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.186 AC: 12622 AN: 68008

Other (OTH) AF: 0.165 AC: 348 AN: 2112

Alfa AF: 0.177 Hom.: 8027

Bravo AF: 0.154

Asia WGS AF: 0.260 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0020
DANN	Benign	0.47
PhyloP100		-6.2
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: rs2073066; hg19: chr6-151197731;