rs1277656894

Variant names:

• chr6-150865950-G-A
• NM_015440.5:c.128G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-150865950-G-A
• chr6-150865950-G-C
• chr6-150865950-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015440.5(MTHFD1L):​c.128G>A​(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,078,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: MTHFD1L NM_015440.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.115

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047126383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.128G>A	p.Arg43Gln	missense_variant	Exon 1 of 28	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.128G>A	p.Arg43Gln	missense_variant	Exon 1 of 28	1	NM_015440.5	ENSP00000356290.3
MTHFD1L	ENST00000367307.8	c.128G>A	p.Arg43Gln	missense_variant	Exon 1 of 8	1		ENSP00000356276.4
MTHFD1L	ENST00000611279.4	c.128G>A	p.Arg43Gln	missense_variant	Exon 1 of 28	5		ENSP00000478253.1
MTHFD1L	ENST00000367308.8	c.5G>A	p.Arg2Gln	missense_variant	Exon 1 of 11	5		ENSP00000356277.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.27e-7 AC: 1 AN: 1078882 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 513272

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.40	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.35	N;.;N
REVEL	Benign	0.0060
Sift	Benign	0.56	T;.;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.16
MutPred		0.19		Loss of methylation at R43 (P = 0.0081);Loss of methylation at R43 (P = 0.0081);Loss of methylation at R43 (P = 0.0081);
MVP		0.048
MPC		0.18
ClinPred		0.068	T
GERP RS		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.019
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-151187086;