rs803424

Positions:

• chr6-150885030-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015440.5(MTHFD1L):​c.543-604C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 152,092 control chromosomes in the GnomAD database, including 27 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 0.017 (27 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.744

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).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.017 (2593/152092) while in subpopulation SAS AF= 0.0249 (120/4818). AF 95% confidence interval is 0.0216. There are 27 homozygotes in gnomad4. There are 1296 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.543-604C>T		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.543-604C>T		intron_variant		1	NM_015440.5	P4

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2595 AN: 151974 Hom.: 27 Cov.: 31

Gnomad AFR AF: 0.00440

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0134

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0247

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0170 AC: 2593 AN: 152092 Hom.: 27 Cov.: 31 AF XY: 0.0174 AC XY: 1296 AN XY: 74358

Gnomad4 AFR AF: 0.00439

Gnomad4 AMR AF: 0.0134

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0213

Gnomad4 SAS AF: 0.0249

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0218

Alfa AF: 0.0162 Hom.: 1

Bravo AF: 0.0154

Asia WGS AF: 0.0160 AC: 55 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	0.23
DANN	Benign	0.51

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: rs803424; hg19: chr6-151206166;