rs754556726

Variant names:

• chr19-7051382-A-G
• rs754556726
• NM_144614.4:c.387A>G

Your query was ambiguous. Multiple possible variants found:

• chr19-7051382-A-G
• chr19-7051382-A-C
• chr19-7051382-A-T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_144614.4(MBD3L2):​c.387A>G​(p.Arg129Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0038 (61 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBD3L2 NM_144614.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.28
• Publications: 0 publications found

Genes affected

MBD3L2 (HGNC:18532): (methyl-CpG binding domain protein 3 like 2) This gene encodes a protein that is related to methyl-CpG-binding proteins but lacks the methyl-CpG binding domain. The protein has been found in germ cell tumors and some somatic tissues. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.11).
• BP6: Variant 19-7051382-A-G is Benign according to our data. Variant chr19-7051382-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2649148.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.28 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144614.4. 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
	MBD3L2	NM_144614.4	MANE Select	c.387A>G	p.Arg129Arg	synonymous	Exon 2 of 2	NP_653215.2	Q8NHZ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3L2	ENST00000381393.3	TSL:1 MANE Select	c.387A>G	p.Arg129Arg	synonymous	Exon 2 of 2	ENSP00000370800.2	Q8NHZ7

Frequencies

GnomAD3 genomes AF: 0.00195 AC: 263 AN: 134868 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000843

Gnomad ASJ AF: 0.000943

Gnomad EAS AF: 0.00132

Gnomad SAS AF: 0.000543

Gnomad FIN AF: 0.000211

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.00225

GnomAD2 exomes AF: 0.00322 AC: 306 AN: 94962 AF XY: 0.00318

Gnomad AFR exome AF: 0.00555

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00170

Gnomad EAS exome AF: 0.00249

Gnomad FIN exome AF: 0.000610

Gnomad NFE exome AF: 0.00350

Gnomad OTH exome AF: 0.00403

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00379 AC: 1933 AN: 510038 Hom.: 61 Cov.: 0 AF XY: 0.00400 AC XY: 1092 AN XY: 272954

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00481 AC: 72 AN: 14976

American (AMR) AF: 0.00494 AC: 156 AN: 31566

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 26 AN: 18070

East Asian (EAS) AF: 0.00243 AC: 75 AN: 30872

South Asian (SAS) AF: 0.00551 AC: 303 AN: 55016

European-Finnish (FIN) AF: 0.000764 AC: 28 AN: 36672

Middle Eastern (MID) AF: 0.00220 AC: 5 AN: 2276

European-Non Finnish (NFE) AF: 0.00403 AC: 1177 AN: 292216

Other (OTH) AF: 0.00321 AC: 91 AN: 28374

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00195 AC: 263 AN: 134976 Hom.: 0 Cov.: 21 AF XY: 0.00199 AC XY: 130 AN XY: 65206

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00396 AC: 148 AN: 37328

American (AMR) AF: 0.000842 AC: 11 AN: 13070

Ashkenazi Jewish (ASJ) AF: 0.000943 AC: 3 AN: 3182

East Asian (EAS) AF: 0.00132 AC: 6 AN: 4552

South Asian (SAS) AF: 0.000544 AC: 2 AN: 3676

European-Finnish (FIN) AF: 0.000211 AC: 2 AN: 9466

Middle Eastern (MID) AF: 0.00365 AC: 1 AN: 274

European-Non Finnish (NFE) AF: 0.00141 AC: 86 AN: 60832

Other (OTH) AF: 0.00222 AC: 4 AN: 1802

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00247 Hom.: 7

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	3.1
DANN	Benign	0.23
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs754556726; hg19: chr19-7051393;