chr6-151101699-C-G

Variant names:

• chr6-151101699-C-G
• rs1047662
• NM_015440.5:c.*205C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015440.5(MTHFD1L):​c.*205C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,584 control chromosomes in the GnomAD database, including 1,146 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 0.11 (1145 hom., cov: 32)
  • Exomes 𝑓: 0.074 (1 hom.)
• Consequence: MTHFD1L NM_015440.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 11 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]

ENSG00000223598 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

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.*205C>G		3_prime_UTR	Exon 28 of 28	NP_056255.2
	MTHFD1L	NM_001242767.2		c.*205C>G		3_prime_UTR	Exon 28 of 28	NP_001229696.1	B7ZM99
	MTHFD1L	NM_001242768.2		c.*205C>G		3_prime_UTR	Exon 28 of 28	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.*205C>G		3_prime_UTR	Exon 28 of 28	ENSP00000356290.3	Q6UB35-1
	MTHFD1L	ENST00000611279.4	TSL:5	c.*205C>G		3_prime_UTR	Exon 28 of 28	ENSP00000478253.1	B7ZM99
	MTHFD1L	ENST00000939695.1		c.*205C>G		3_prime_UTR	Exon 28 of 28	ENSP00000609754.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16413 AN: 152036 Hom.: 1140 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0744 AC: 32 AN: 430 Hom.: 1 Cov.: 0 AF XY: 0.0654 AC XY: 17 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0755 AC: 32 AN: 424

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.108 AC: 16427 AN: 152154 Hom.: 1145 Cov.: 32 AF XY: 0.113 AC XY: 8427 AN XY: 74374

African (AFR) AF: 0.155 AC: 6436 AN: 41486

American (AMR) AF: 0.0760 AC: 1162 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 437 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1094 AN: 5176

South Asian (SAS) AF: 0.286 AC: 1376 AN: 4818

European-Finnish (FIN) AF: 0.0812 AC: 859 AN: 10582

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4764 AN: 68002

Other (OTH) AF: 0.104 AC: 220 AN: 2116

Alfa AF: 0.0298 Hom.: 23

Bravo AF: 0.106

Asia WGS AF: 0.227 AC: 787 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs1047662; hg19: chr6-151422835;