rs12525353

Positions:

• chr6-150978896-C-A

Variant summary

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

The NM_015440.5(MTHFD1L):​c.2125+6838C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 152,234 control chromosomes in the GnomAD database, including 36 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 0.019 (36 hom., cov: 32)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221

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=-0.89).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.019 (2898/152234) while in subpopulation NFE AF= 0.0292 (1984/68014). AF 95% confidence interval is 0.0281. There are 36 homozygotes in gnomad4. There are 1403 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.2125+6838C>A		intron_variant		ENST00000367321.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2125+6838C>A		intron_variant		1	NM_015440.5	P4
MTHFD1L	ENST00000611279.4	c.2128+6838C>A		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.1930+6838C>A		intron_variant		5
MTHFD1L	ENST00000478643.1	n.112-6143C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2896 AN: 152116 Hom.: 36 Cov.: 32

Gnomad AFR AF: 0.00362

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0198

Gnomad ASJ AF: 0.0485

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0225

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

GnomAD4 genome AF: 0.0190 AC: 2898 AN: 152234 Hom.: 36 Cov.: 32 AF XY: 0.0188 AC XY: 1403 AN XY: 74440

Gnomad4 AFR AF: 0.00361

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.0485

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0292

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0296 Hom.: 9

Bravo AF: 0.0181

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.56

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: rs12525353; hg19: chr6-151300032;