rs572987

Variant names:

• chr4-74219929-C-T
• rs572987
• NM_001144978.3:c.713-5373C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144978.3(MTHFD2L):​c.713-5373C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.935 in 152,156 control chromosomes in the GnomAD database, including 66,887 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 0.93 (66887 hom., cov: 32)
• Consequence: MTHFD2L NM_001144978.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262
• Publications: 3 publications found

Genes affected

MTHFD2L (HGNC:31865): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like) Predicted to enable methenyltetrahydrofolate cyclohydrolase activity; methylenetetrahydrofolate dehydrogenase (NAD+) activity; and methylenetetrahydrofolate dehydrogenase (NADP+) activity. Predicted to be involved in tetrahydrofolate interconversion. Predicted to be located in mitochondrial matrix. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.982 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144978.3. 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
	MTHFD2L	NM_001144978.3	MANE Select	c.713-5373C>T		intron	N/A	NP_001138450.1	Q9H903-4
	MTHFD2L	NM_001004346.4		c.539-5373C>T		intron	N/A	NP_001004346.2	Q9H903-1
	MTHFD2L	NM_001351310.2		c.539-5373C>T		intron	N/A	NP_001338239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD2L	ENST00000325278.7	TSL:5 MANE Select	c.713-5373C>T		intron	N/A	ENSP00000321984.7	Q9H903-4
	MTHFD2L	ENST00000433372.5	TSL:1	n.684-5373C>T		intron	N/A
	MTHFD2L	ENST00000395759.6	TSL:5	c.713-5373C>T		intron	N/A	ENSP00000379108.2	Q9H903-4

Frequencies

GnomAD3 genomes AF: 0.935 AC: 142151 AN: 152038 Hom.: 66869 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.953

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.991

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.988

Gnomad OTH AF: 0.945

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

GnomAD4 genome AF: 0.935 AC: 142223 AN: 152156 Hom.: 66887 Cov.: 32 AF XY: 0.935 AC XY: 69522 AN XY: 74392

African (AFR) AF: 0.819 AC: 33981 AN: 41498

American (AMR) AF: 0.953 AC: 14537 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3459 AN: 3472

East Asian (EAS) AF: 0.947 AC: 4915 AN: 5188

South Asian (SAS) AF: 0.923 AC: 4456 AN: 4828

European-Finnish (FIN) AF: 0.991 AC: 10523 AN: 10618

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.988 AC: 67160 AN: 67972

Other (OTH) AF: 0.944 AC: 1996 AN: 2114

Alfa AF: 0.968 Hom.: 35169

Bravo AF: 0.928

Asia WGS AF: 0.908 AC: 3157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.75
PhyloP100		0.26
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs572987;

hg19: chr4-75085646;