rs11646114

Variant names:

• chr16-86550168-T-A
• rs11646114
• NM_001159377.2:c.238-1591A>T

Variant summary

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

The NM_001159377.2(MTHFSD):​c.238-1591A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 152,318 control chromosomes in the GnomAD database, including 218 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 0.042 (218 hom., cov: 34)
• Consequence: MTHFSD NM_001159377.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 2 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 (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159377.2. 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
	MTHFSD	NM_001159377.2	MANE Select	c.238-1591A>T		intron	N/A	NP_001152849.1
	MTHFSD	NM_001159378.2		c.238-1591A>T		intron	N/A	NP_001152850.1
	MTHFSD	NM_001159379.2		c.235-1591A>T		intron	N/A	NP_001152851.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFSD	ENST00000360900.11	TSL:1 MANE Select	c.238-1591A>T		intron	N/A	ENSP00000354152.6
	MTHFSD	ENST00000381214.9	TSL:1	c.238-1591A>T		intron	N/A	ENSP00000370612.5
	MTHFSD	ENST00000543303.6	TSL:1	c.235-1591A>T		intron	N/A	ENSP00000444003.2

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6421 AN: 152200 Hom.: 218 Cov.: 34

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.0811

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0898

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0564

Gnomad OTH AF: 0.0401

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

GnomAD4 genome AF: 0.0421 AC: 6414 AN: 152318 Hom.: 218 Cov.: 34 AF XY: 0.0430 AC XY: 3204 AN XY: 74476

African (AFR) AF: 0.00962 AC: 400 AN: 41580

American (AMR) AF: 0.0442 AC: 677 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 281 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4830

European-Finnish (FIN) AF: 0.0898 AC: 953 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0564 AC: 3840 AN: 68030

Other (OTH) AF: 0.0397 AC: 84 AN: 2116

Alfa AF: 0.0497 Hom.: 25

Bravo AF: 0.0375

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.2
DANN	Benign	0.61
PhyloP100		1.0
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

Other links and lift over

dbSNP: rs11646114; hg19: chr16-86583774;