rs6933598

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015440.5(MTHFD1L):​c.1394-65C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,550,708 control chromosomes in the GnomAD database, including 66,617 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 0.35 ( 11386 hom., cov: 32)
Exomes 𝑓: 0.27 ( 55231 hom. )

Consequence

MTHFD1L
NM_015440.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.526
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MTHFD1LNM_015440.5 linkuse as main transcriptc.1394-65C>G intron_variant ENST00000367321.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MTHFD1LENST00000367321.8 linkuse as main transcriptc.1394-65C>G intron_variant 1 NM_015440.5 P4Q6UB35-1
MTHFD1LENST00000611279.4 linkuse as main transcriptc.1397-65C>G intron_variant 5 A1
MTHFD1LENST00000618312.4 linkuse as main transcriptc.1199-65C>G intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.352
AC:
53413
AN:
151774
Hom.:
11356
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.592
Gnomad AMI
AF:
0.191
Gnomad AMR
AF:
0.374
Gnomad ASJ
AF:
0.176
Gnomad EAS
AF:
0.0236
Gnomad SAS
AF:
0.275
Gnomad FIN
AF:
0.219
Gnomad MID
AF:
0.218
Gnomad NFE
AF:
0.265
Gnomad OTH
AF:
0.327
GnomAD4 exome
AF:
0.270
AC:
378194
AN:
1398816
Hom.:
55231
AF XY:
0.269
AC XY:
186526
AN XY:
693310
show subpopulations
Gnomad4 AFR exome
AF:
0.608
Gnomad4 AMR exome
AF:
0.381
Gnomad4 ASJ exome
AF:
0.182
Gnomad4 EAS exome
AF:
0.0168
Gnomad4 SAS exome
AF:
0.285
Gnomad4 FIN exome
AF:
0.222
Gnomad4 NFE exome
AF:
0.269
Gnomad4 OTH exome
AF:
0.266
GnomAD4 genome
AF:
0.352
AC:
53508
AN:
151892
Hom.:
11386
Cov.:
32
AF XY:
0.349
AC XY:
25943
AN XY:
74240
show subpopulations
Gnomad4 AFR
AF:
0.592
Gnomad4 AMR
AF:
0.375
Gnomad4 ASJ
AF:
0.176
Gnomad4 EAS
AF:
0.0231
Gnomad4 SAS
AF:
0.276
Gnomad4 FIN
AF:
0.219
Gnomad4 NFE
AF:
0.265
Gnomad4 OTH
AF:
0.326
Alfa
AF:
0.315
Hom.:
1125
Bravo
AF:
0.371
Asia WGS
AF:
0.176
AC:
614
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.69
DANN
Benign
0.75

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6933598; hg19: chr6-151259770; COSMIC: COSV63365362; COSMIC: COSV63365362; API