rs9397033

chr6-151093956-T-Achr6-151093956-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MTHFD1L	NM_015440.5	c.*31+1369T>A		intron_variant		ENST00000367321.8
LOC124901432	XR_007059813.1	n.342-5576A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTHFD1L	ENST00000367321.8	c.*31+1369T>A		intron_variant		1	NM_015440.5	P4
	ENST00000415477.1	n.576-5576A>T		intron_variant, non_coding_transcript_variant		5
MTHFD1L	ENST00000611279.4	c.*31+1369T>A		intron_variant		5		A1
MTHFD1L	ENST00000618312.4	c.*31+1369T>A		intron_variant		5

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

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.322

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

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

LitVar

Other links and lift over

dbSNP: rs9397033; hg19: chr6-151415092; COSMIC: COSV66224791;