rs6557106

Positions:

• chr6-150957588-C-T

Variant summary

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

The NM_015440.5(MTHFD1L):​c.1803+1517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,034 control chromosomes in the GnomAD database, including 36,529 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 0.69 (36529 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

Genes affected

MTHFD1L (HGNC:21055): (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like) The protein encoded by this gene is involved in the synthesis of tetrahydrofolate (THF) in the mitochondrion. THF is important in the de novo synthesis of purines and thymidylate and in the regeneration of methionine from homocysteine. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.1803+1517C>T		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1803+1517C>T		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.1806+1517C>T		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.1608+1517C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104804 AN: 151916 Hom.: 36468 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.690 AC: 104930 AN: 152034 Hom.: 36529 Cov.: 32 AF XY: 0.685 AC XY: 50915 AN XY: 74316

Gnomad4 AFR AF: 0.750

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.507

Gnomad4 SAS AF: 0.504

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.673

Gnomad4 OTH AF: 0.694

Alfa AF: 0.687 Hom.: 6062

Bravo AF: 0.701

Asia WGS AF: 0.556 AC: 1933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.2
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs6557106; hg19: chr6-151278724; COSMIC: COSV66227099;