rs803424

Variant names:

• chr6-150885030-C-T
• rs803424
• NM_015440.5:c.543-604C>T

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.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
• 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=-0.98).
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015440.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	NM_015440.5	MANE Select	c.543-604C>T		intron	N/A	NP_056255.2
	MTHFD1L	NM_001242767.2		c.543-604C>T		intron	N/A	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.345-604C>T		intron	N/A	NP_001229697.1	A0A087WVM4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTHFD1L	ENST00000367321.8	TSL:1 MANE Select	c.543-604C>T		intron	N/A	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000367307.8	TSL:1	c.543-604C>T		intron	N/A	ENSP00000356276.4	Q6UB35-2
	MTHFD1L	ENST00000611279.4	TSL:5	c.543-604C>T		intron	N/A	ENSP00000478253.1	B7ZM99

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

African (AFR) AF: 0.00439 AC: 182 AN: 41474

American (AMR) AF: 0.0134 AC: 204 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3466

East Asian (EAS) AF: 0.0213 AC: 110 AN: 5174

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4818

European-Finnish (FIN) AF: 0.0264 AC: 279 AN: 10570

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0225 AC: 1532 AN: 67998

Other (OTH) AF: 0.0218 AC: 46 AN: 2108

Alfa AF: 0.0203 Hom.: 43

Bravo AF: 0.0154

Asia WGS AF: 0.0160 AC: 55 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.23
DANN	Benign	0.51
PhyloP100		-0.74
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: rs803424; hg19: chr6-151206166;