12-57525776-C-T

Position:

• chr12-57525776-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052897.4(MBD6):​c.808C>T​(p.Pro270Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 31)
• Consequence: MBD6 NM_052897.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.563

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10164121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD6	NM_052897.4	c.808C>T	p.Pro270Ser	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.808C>T	p.Pro270Ser	missense_variant	6/13	1	NM_052897.4	ENSP00000347896	P1
MBD6	ENST00000552659.1	c.365-535C>T		intron_variant		3		ENSP00000446834

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

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

May 08, 2024

The c.808C>T (p.P270S) alteration is located in exon 6 (coding exon 4) of the MBD6 gene. This alteration results from a C to T substitution at nucleotide position 808, causing the proline (P) at amino acid position 270 to be replaced by a serine (S). 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	0.078
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.97	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.025
Sift	Benign	0.061	T
Sift4G	Uncertain	0.059	T
Polyphen		0.70	P
Vest4		0.30
MutPred		0.30		Gain of catalytic residue at P273 (P = 8e-04);
MVP		0.043
MPC		0.046
ClinPred		0.093	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.036
gMVP		0.19

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: chr12-57919559;