12-57525870-T-A

Position:

• chr12-57525870-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052897.4(MBD6):​c.902T>A​(p.Leu301Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: MBD6 NM_052897.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD6	NM_052897.4	c.902T>A	p.Leu301Gln	missense_variant	6/13	ENST00000355673.8	NP_443129.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD6	ENST00000355673.8	c.902T>A	p.Leu301Gln	missense_variant	6/13	1	NM_052897.4	ENSP00000347896	P1
MBD6	ENST00000552659.1	c.365-441T>A		intron_variant		3		ENSP00000446834

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.902T>A (p.L301Q) alteration is located in exon 6 (coding exon 4) of the MBD6 gene. This alteration results from a T to A substitution at nucleotide position 902, causing the leucine (L) at amino acid position 301 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Benign	0.94
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0074	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.98	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.32	T
Polyphen		1.0	D
Vest4		0.78
MutPred		0.30		Gain of catalytic residue at G302 (P = 5e-04);
MVP		0.043
MPC		0.047
ClinPred		0.31	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.34

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: chr12-57919653;