6-150899109-A-G

Variant names:

• chr6-150899109-A-G
• rs803419
• NM_015440.5:c.781-6541A>G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.781-6541A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 448,792 control chromosomes in the GnomAD database, including 65,886 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 0.56 (24021 hom., cov: 32)
  • Exomes 𝑓: 0.52 (41865 hom.)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.781-6541A>G		intron_variant	Intron 7 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.781-6541A>G		intron_variant	Intron 7 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84457 AN: 151918 Hom.: 23996 Cov.: 32

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.561

GnomAD4 exome AF: 0.522 AC: 154911 AN: 296756 Hom.: 41865 AF XY: 0.522 AC XY: 73999 AN XY: 141764

African (AFR) AF: 0.522 AC: 2762 AN: 5288

American (AMR) AF: 0.631 AC: 328 AN: 520

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 894 AN: 1826

East Asian (EAS) AF: 0.802 AC: 1065 AN: 1328

South Asian (SAS) AF: 0.708 AC: 4188 AN: 5916

European-Finnish (FIN) AF: 0.563 AC: 90 AN: 160

Middle Eastern (MID) AF: 0.400 AC: 800 AN: 2000

European-Non Finnish (NFE) AF: 0.517 AC: 139451 AN: 269850

Other (OTH) AF: 0.540 AC: 5333 AN: 9868

GnomAD4 genome AF: 0.556 AC: 84528 AN: 152036 Hom.: 24021 Cov.: 32 AF XY: 0.567 AC XY: 42158 AN XY: 74314

African (AFR) AF: 0.523 AC: 21692 AN: 41468

American (AMR) AF: 0.653 AC: 9973 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3468

East Asian (EAS) AF: 0.816 AC: 4231 AN: 5182

South Asian (SAS) AF: 0.726 AC: 3504 AN: 4826

European-Finnish (FIN) AF: 0.622 AC: 6567 AN: 10552

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.515 AC: 35015 AN: 67958

Other (OTH) AF: 0.562 AC: 1183 AN: 2104

Alfa AF: 0.534 Hom.: 2768

Bravo AF: 0.553

Asia WGS AF: 0.728 AC: 2534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.58
DANN	Benign	0.80
PhyloP100		-0.32
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: rs803419; hg19: chr6-151220245;