12-57525746-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052897.4(MBD6):​c.778C>T​(p.Leu260Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L260V) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MBD6
NM_052897.4 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.83
Variant links:
Genes affected
MBD6 (HGNC:20445): (methyl-CpG binding domain protein 6) Enables chromatin binding activity. Located in chromocenter; fibrillar center; and nucleoplasm. Implicated in autism spectrum disorder. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18393484).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MBD6NM_052897.4 linkc.778C>T p.Leu260Phe missense_variant Exon 6 of 13 ENST00000355673.8 NP_443129.3 Q96DN6A0A024RBA3Q6P0P0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MBD6ENST00000355673.8 linkc.778C>T p.Leu260Phe missense_variant Exon 6 of 13 1 NM_052897.4 ENSP00000347896.3 Q96DN6
MBD6ENST00000552659.1 linkc.365-565C>T intron_variant Intron 3 of 4 3 ENSP00000446834.1 H0YHD1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461840
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Benign
0.031
T
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.74
T
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.080
Sift
Uncertain
0.0050
D
Sift4G
Benign
0.19
T
Polyphen
0.98
D
Vest4
0.34
MutPred
0.31
Gain of catalytic residue at P258 (P = 0);
MVP
0.043
MPC
0.049
ClinPred
0.40
T
GERP RS
2.6
Varity_R
0.15
gMVP
0.11

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: chr12-57919529; API