rs3751797

Positions:

• chr16-86533886-A-T

Variant summary

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

The NM_001159377.2(MTHFSD):​c.682-1405T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,074 control chromosomes in the GnomAD database, including 9,056 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 0.33 (9055 hom., cov: 33)
  • Exomes 𝑓: 0.21 (1 hom.)
• Consequence: MTHFSD NM_001159377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

Genes affected

MTHFSD (HGNC:25778): (methenyltetrahydrofolate synthetase domain containing) Enables RNA binding activity. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MTHFSD (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTHFSD	NM_001159377.2	c.682-1405T>A		intron_variant		ENST00000360900.11	NP_001152849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTHFSD	ENST00000360900.11	c.682-1405T>A		intron_variant		1	NM_001159377.2	ENSP00000354152.6

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50559 AN: 151926 Hom.: 9024 Cov.: 33

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.214 AC: 6 AN: 28 Hom.: 1 AF XY: 0.227 AC XY: 5 AN XY: 22

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.333 AC: 50643 AN: 152046 Hom.: 9055 Cov.: 33 AF XY: 0.342 AC XY: 25387 AN XY: 74320

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.519

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.321

Alfa AF: 0.287 Hom.: 860

Bravo AF: 0.348

Asia WGS AF: 0.453 AC: 1577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.1
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751797; hg19: chr16-86567492;