rs9397033

Variant names:

• chr6-151093956-T-A
• rs9397033
• NM_015440.5:c.*31+1369T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151093956-T-A
• chr6-151093956-T-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.*31+1369T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 151,936 control chromosomes in the GnomAD database, including 7,580 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 0.30 (7580 hom., cov: 31)
• Consequence: MTHFD1L NM_015440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTHFD1L	NM_015440.5	c.*31+1369T>A		intron_variant	Intron 27 of 27	ENST00000367321.8	NP_056255.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.*31+1369T>A		intron_variant	Intron 27 of 27	1	NM_015440.5	ENSP00000356290.3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45338 AN: 151816 Hom.: 7581 Cov.: 31

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.298 AC: 45343 AN: 151936 Hom.: 7580 Cov.: 31 AF XY: 0.294 AC XY: 21848 AN XY: 74236

African (AFR) AF: 0.144 AC: 5953 AN: 41472

American (AMR) AF: 0.339 AC: 5180 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3468

East Asian (EAS) AF: 0.569 AC: 2918 AN: 5132

South Asian (SAS) AF: 0.241 AC: 1158 AN: 4806

European-Finnish (FIN) AF: 0.276 AC: 2911 AN: 10556

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24589 AN: 67932

Other (OTH) AF: 0.322 AC: 679 AN: 2106

Alfa AF: 0.333 Hom.: 1209

Bravo AF: 0.305

Asia WGS AF: 0.355 AC: 1236 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	0.065
DANN	Benign	0.78
PhyloP100		-2.2
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: rs9397033; hg19: chr6-151415092; COSMIC: COSV66224791;