rs685487

Positions:

• chr15-79843787-A-C
• chr15-79843787-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006441.4(MTHFS):​c.*1423T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: MTHFS NM_006441.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

Genes affected

MTHFS (HGNC:7437): (methenyltetrahydrofolate synthetase) The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

ST20-MTHFS (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFS	NM_006441.4	c.*1423T>G		3_prime_UTR_variant	3/3	ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2	c.*1423T>G		3_prime_UTR_variant	4/4		NP_001186689.1
MTHFS	NM_001199758.1	c.*1423T>G		3_prime_UTR_variant	3/3		NP_001186687.1
MTHFS	NR_037654.2	n.2142T>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFS	ENST00000258874.4	c.*1423T>G		3_prime_UTR_variant	3/3	1	NM_006441.4	ENSP00000258874	P1
	ENST00000567415.1	n.518T>G		non_coding_transcript_exon_variant	1/1
MTHFS	ENST00000560261.1	c.*52+1371T>G		intron_variant, NMD_transcript_variant		3		ENSP00000454318

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs685487; hg19: chr15-80136129;