15-79843787-A-G

Position:

• chr15-79843787-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006441.4(MTHFS):​c.*1423T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,124 control chromosomes in the GnomAD database, including 9,565 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 0.34 (9565 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFS	NM_006441.4	c.*1423T>C		3_prime_UTR_variant	3/3	ENST00000258874.4	NP_006432.1
ST20-MTHFS	NM_001199760.2	c.*1423T>C		3_prime_UTR_variant	4/4		NP_001186689.1
MTHFS	NM_001199758.1	c.*1423T>C		3_prime_UTR_variant	3/3		NP_001186687.1
MTHFS	NR_037654.2	n.2142T>C		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>C		3_prime_UTR_variant	3/3	1	NM_006441.4	ENSP00000258874	P1
	ENST00000567415.1	n.518T>C		non_coding_transcript_exon_variant	1/1
MTHFS	ENST00000560261.1	c.*52+1371T>C		intron_variant, NMD_transcript_variant		3		ENSP00000454318

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51419 AN: 152006 Hom.: 9563 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.333

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.338 AC: 51436 AN: 152124 Hom.: 9565 Cov.: 32 AF XY: 0.342 AC XY: 25432 AN XY: 74352

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.417

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.332

Alfa AF: 0.371 Hom.: 21394

Bravo AF: 0.332

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.74

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;