20-62799548-G-T

Variant names:

• chr20-62799548-G-T
• rs767307186
• NM_018270.6:c.520G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018270.6(MRGBP):​c.520G>T​(p.Ala174Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A174T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MRGBP NM_018270.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

Genes affected

MRGBP (HGNC:15866): (MRG domain binding protein) Predicted to be involved in histone acetylation and regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037852526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRGBP	NM_018270.6	c.520G>T	p.Ala174Ser	missense_variant	Exon 5 of 5	ENST00000370487.5	NP_060740.1
MRGBP	NR_136405.2	n.693G>T		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRGBP	ENST00000370487.5	c.520G>T	p.Ala174Ser	missense_variant	Exon 5 of 5	1	NM_018270.6	ENSP00000359518.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.027
Sift	Benign	0.39	T
Sift4G	Benign	0.85	T
Polyphen		0.026	B
Vest4		0.050
MutPred		0.19		Gain of phosphorylation at A174 (P = 0.0023);
MVP		0.23
MPC		0.98
ClinPred		0.090	T
GERP RS		3.5
Varity_R		0.045
gMVP		0.052

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

LitVar

Other links and lift over

dbSNP: rs767307186; hg19: chr20-61430900;