rs139232639

Variant names:

• chr12-57525746-C-G
• rs139232639
• NM_052897.4:c.778C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-57525746-C-G
• chr12-57525746-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_052897.4(MBD6):​c.778C>G​(p.Leu260Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,614,056 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00088 (31 hom.)
• Consequence: MBD6 NM_052897.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83
• Publications: 1 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030482411).
• BP6: Variant 12-57525746-C-G is Benign according to our data. Variant chr12-57525746-C-G is described in ClinVar as Benign. ClinVar VariationId is 720957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00127 (193/152216) while in subpopulation EAS AF = 0.0271 (140/5164). AF 95% confidence interval is 0.0235. There are 5 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

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.778C>G	p.Leu260Val	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.778C>G	p.Leu260Val	missense	Exon 6 of 13	ENSP00000347896.3	Q96DN6
	MBD6	ENST00000861014.1		c.778C>G	p.Leu260Val	missense	Exon 6 of 13	ENSP00000531073.1
	MBD6	ENST00000861015.1		c.778C>G	p.Leu260Val	missense	Exon 5 of 12	ENSP00000531074.1

Frequencies

GnomAD3 genomes AF: 0.00119 AC: 181 AN: 152100 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00237 AC: 595 AN: 251058 AF XY: 0.00211

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0304

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.000882 AC: 1290 AN: 1461840 Hom.: 31 Cov.: 35 AF XY: 0.000870 AC XY: 633 AN XY: 727234

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000895 AC: 4 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0264 AC: 1048 AN: 39700

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000306 AC: 34 AN: 1111990

Other (OTH) AF: 0.00263 AC: 159 AN: 60394

GnomAD4 genome AF: 0.00127 AC: 193 AN: 152216 Hom.: 5 Cov.: 31 AF XY: 0.00128 AC XY: 95 AN XY: 74418

African (AFR) AF: 0.0000722 AC: 3 AN: 41532

American (AMR) AF: 0.00137 AC: 21 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.0271 AC: 140 AN: 5164

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67974

Other (OTH) AF: 0.00900 AC: 19 AN: 2110

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.00131

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00244 AC: 296

Asia WGS AF: 0.0370 AC: 128 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.062
Sift	Uncertain	0.0050	D
Sift4G	Benign	1.0	T
Polyphen		0.86	P
Vest4		0.29
MVP		0.043
MPC		0.046
ClinPred		0.031	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.10
Mutation Taster		=98/2	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

dbSNP: rs139232639; hg19: chr12-57919529;