chr17-76733148-T-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_001080510.5(METTL23):ā€‹c.255T>Gā€‹(p.Ser85=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00083 ( 0 hom., cov: 33)
Exomes š‘“: 0.000086 ( 0 hom. )

Consequence

METTL23
NM_001080510.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.71
Variant links:
Genes affected
METTL23 (HGNC:26988): (methyltransferase 23, arginine) The protein encoded by this gene functions as a transcription factor regulator in the transcriptional pathway for human cognition. It is a partner of the alpha subunit of the GA-binding protein transcription factor. Mutations in this gene cause mild autosomal recessive intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-76733148-T-G is Benign according to our data. Variant chr17-76733148-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 737135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-2.71 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000827 (126/152332) while in subpopulation AFR AF= 0.00267 (111/41584). AF 95% confidence interval is 0.00227. There are 0 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
METTL23NM_001080510.5 linkuse as main transcriptc.255T>G p.Ser85= synonymous_variant 3/5 ENST00000341249.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
METTL23ENST00000341249.11 linkuse as main transcriptc.255T>G p.Ser85= synonymous_variant 3/51 NM_001080510.5 P1Q86XA0-1

Frequencies

GnomAD3 genomes
AF:
0.000828
AC:
126
AN:
152214
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00268
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000786
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000173
AC:
43
AN:
249000
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
135082
show subpopulations
Gnomad AFR exome
AF:
0.00259
Gnomad AMR exome
AF:
0.0000870
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000855
AC:
125
AN:
1461602
Hom.:
0
Cov.:
33
AF XY:
0.0000701
AC XY:
51
AN XY:
727060
show subpopulations
Gnomad4 AFR exome
AF:
0.00311
Gnomad4 AMR exome
AF:
0.000157
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:
0.00000180
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000827
AC:
126
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.000859
AC XY:
64
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00267
Gnomad4 AMR
AF:
0.000785
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000723
Hom.:
0
Bravo
AF:
0.000994

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoJun 14, 2019- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
2.4
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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: rs370380855; hg19: chr17-74729230; API