5-56923260-A-T

Position:

• chr5-56923260-A-T

Variant summary

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

The NM_001297599.2(MIER3):​c.1521T>A​(p.Asn507Lys) 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. 15/21 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)
• Consequence: MIER3 NM_001297599.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

Genes affected

MIER3 (HGNC:26678): (MIER family member 3) Predicted to enable histone deacetylase binding activity and transcription corepressor activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

SETD9 (HGNC:28508): (SET domain containing 9) Predicted to enable lysine N-methyltransferase activity. Predicted to be involved in regulation of signal transduction by p53 class mediator. Predicted to be located in nucleoplasm. [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=0.098642886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIER3	NM_001297599.2	c.1521T>A	p.Asn507Lys	missense_variant	13/13	ENST00000381199.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIER3	ENST00000381199.8	c.1521T>A	p.Asn507Lys	missense_variant	13/13	1	NM_001297599.2	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.95
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.099	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.95	D;D;D;D;D
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N;N;N;N
REVEL	Benign	0.023
Sift	Benign	0.14	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.33	B;B;B;.
Vest4		0.45
MutPred		0.43		.;.;Gain of methylation at N507 (P = 0.0127);.;
MVP		0.12
MPC		0.66
ClinPred		0.064	T
GERP RS		1.8
Varity_R		0.048
gMVP		0.25

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: chr5-56219087;