NM_052897.4:c.671C>A

Variant names:

• chr12-57525639-C-A
• NM_052897.4:c.671C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052897.4(MBD6):​c.671C>A​(p.Ala224Asp) 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. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MBD6 NM_052897.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2828791).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052897.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD6	NM_052897.4	MANE Select	c.671C>A	p.Ala224Asp	missense	Exon 6 of 13	NP_443129.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD6	ENST00000355673.8	TSL:1 MANE Select	c.671C>A	p.Ala224Asp	missense	Exon 6 of 13	ENSP00000347896.3	Q96DN6
	MBD6	ENST00000861014.1		c.671C>A	p.Ala224Asp	missense	Exon 6 of 13	ENSP00000531073.1
	MBD6	ENST00000861015.1		c.671C>A	p.Ala224Asp	missense	Exon 5 of 12	ENSP00000531074.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.1
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.34	T
Polyphen		0.49	P
Vest4		0.71
MutPred		0.27		Gain of catalytic residue at N223 (P = 0)
MVP		0.043
MPC		0.062
ClinPred		0.36	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.29
gMVP		0.24
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

hg19: chr12-57919422;