rs12525353

Variant names:

• chr6-150978896-C-A
• rs12525353
• NM_015440.5:c.2125+6838C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.89).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.2125+6838C>A		intron_variant	Intron 20 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.2125+6838C>A		intron_variant	Intron 20 of 27	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000611279.4	c.2128+6838C>A		intron_variant	Intron 20 of 27	5		ENSP00000478253.1
MTHFD1L	ENST00000618312.4	c.1930+6838C>A		intron_variant	Intron 20 of 27	5		ENSP00000479539.1
MTHFD1L	ENST00000478643.1	n.112-6143C>A		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.00361 AC: 150 AN: 41552

American (AMR) AF: 0.0198 AC: 302 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0485 AC: 168 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.0104 AC: 50 AN: 4824

European-Finnish (FIN) AF: 0.0119 AC: 126 AN: 10604

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0292 AC: 1984 AN: 68014

Other (OTH) AF: 0.0227 AC: 48 AN: 2114

Alfa AF: 0.0287 Hom.: 24

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
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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: rs12525353; hg19: chr6-151300032;