rs6557106

Variant names:

• chr6-150957588-C-T
• rs6557106
• NM_015440.5:c.1803+1517C>T

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.1803+1517C>T		intron_variant	Intron 17 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1803+1517C>T		intron_variant	Intron 17 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.1806+1517C>T		intron_variant	Intron 17 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.1608+1517C>T		intron_variant	Intron 17 of 27	5		ENSP00000479539.1

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

African (AFR) AF: 0.750 AC: 31109 AN: 41502

American (AMR) AF: 0.745 AC: 11371 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 2404 AN: 3470

East Asian (EAS) AF: 0.507 AC: 2623 AN: 5178

South Asian (SAS) AF: 0.504 AC: 2426 AN: 4816

European-Finnish (FIN) AF: 0.673 AC: 7094 AN: 10546

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45704 AN: 67942

Other (OTH) AF: 0.694 AC: 1464 AN: 2110

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
PhyloP100		-0.35
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: rs6557106; hg19: chr6-151278724; COSMIC: COSV66227099;