rs6933598

Positions:

• chr6-150938634-C-G

Variant summary

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

The NM_015440.5(MTHFD1L):​c.1394-65C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,550,708 control chromosomes in the GnomAD database, including 66,617 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 0.35 (11386 hom., cov: 32)
  • Exomes 𝑓: 0.27 (55231 hom.)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.1394-65C>G		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.1394-65C>G		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.1397-65C>G		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.1199-65C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53413 AN: 151774 Hom.: 11356 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.327

GnomAD4 exome AF: 0.270 AC: 378194 AN: 1398816 Hom.: 55231 AF XY: 0.269 AC XY: 186526 AN XY: 693310

Gnomad4 AFR exome AF: 0.608

Gnomad4 AMR exome AF: 0.381

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.0168

Gnomad4 SAS exome AF: 0.285

Gnomad4 FIN exome AF: 0.222

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.352 AC: 53508 AN: 151892 Hom.: 11386 Cov.: 32 AF XY: 0.349 AC XY: 25943 AN XY: 74240

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0231

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.265

Gnomad4 OTH AF: 0.326

Alfa AF: 0.315 Hom.: 1125

Bravo AF: 0.371

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.75

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: rs6933598; hg19: chr6-151259770; COSMIC: COSV63365362; COSMIC: COSV63365362;