rs3751797

Variant names:

• chr16-86533886-A-T
• rs3751797
• NM_001159377.2:c.682-1405T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

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 (EAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFSD	NM_001159377.2	c.682-1405T>A		intron_variant	Intron 7 of 7	ENST00000360900.11	NP_001152849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFSD	ENST00000360900.11	c.682-1405T>A		intron_variant	Intron 7 of 7	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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 5 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.405 AC: 16787 AN: 41454

American (AMR) AF: 0.440 AC: 6722 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 834 AN: 3468

East Asian (EAS) AF: 0.519 AC: 2680 AN: 5160

South Asian (SAS) AF: 0.449 AC: 2167 AN: 4826

European-Finnish (FIN) AF: 0.296 AC: 3133 AN: 10574

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17279 AN: 67956

Other (OTH) AF: 0.321 AC: 679 AN: 2112

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
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3751797; hg19: chr16-86567492;