rs887545705

Variant names:

• chr2-42656241-G-A
• rs887545705
• NM_001330442.2:c.541G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-42656241-G-A
• chr2-42656241-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 1P and 5B. PP2 BP4 BS2

The NM_001330442.2(MTA3):​c.541G>A​(p.Val181Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MTA3 NM_001330442.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

Genes affected

MTA3 (HGNC:23784): (metastasis associated 1 family member 3) Predicted to enable histone deacetylase binding activity; transcription coactivator activity; and transcription corepressor activity. Involved in negative regulation of transcription, DNA-templated. Located in nucleoplasm. Part of NuRD complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.65794 (below the threshold of 3.09). Trascript score misZ: -0.24302 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.32391548).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330442.2. 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
	MTA3	NM_001330442.2	MANE Select	c.541G>A	p.Val181Ile	missense	Exon 7 of 17	NP_001317371.1	Q9BTC8-1
	MTA3	NM_001330443.2		c.541G>A	p.Val181Ile	missense	Exon 7 of 17	NP_001317372.1
	MTA3	NM_001282755.2		c.373G>A	p.Val125Ile	missense	Exon 8 of 18	NP_001269684.1	F6RRE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTA3	ENST00000405094.2	TSL:5 MANE Select	c.541G>A	p.Val181Ile	missense	Exon 7 of 17	ENSP00000385823.1	Q9BTC8-1
	MTA3	ENST00000406652.5	TSL:1	c.373G>A	p.Val125Ile	missense	Exon 7 of 17	ENSP00000384249.1	F6RRE2
	MTA3	ENST00000407270.7	TSL:1	c.541G>A	p.Val181Ile	missense	Exon 7 of 14	ENSP00000385045.3	Q9BTC8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249174 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461524 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 727034

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111772

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.054
Sift	Benign	0.15	T
Sift4G	Benign	0.20	T
Polyphen		0.0030	B
Vest4		0.19
MutPred		0.50		Loss of methylation at K124 (P = 0.0781)
MVP		0.33
MPC		0.14
ClinPred		0.29	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.056
gMVP		0.17
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs887545705; hg19: chr2-42883381;