16-4634447-G-C

Variant names:

• chr16-4634447-G-C
• rs1659506
• NM_015246.4:c.88+9399G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015246.4(MGRN1):​c.88+9399G>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGRN1 NM_015246.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77
• Publications: 7 publications found

Genes affected

MGRN1 (HGNC:20254): (mahogunin ring finger 1) Enables ubiquitin-protein transferase activity. Involved in endosome to lysosome transport; negative regulation of signal transduction; and protein monoubiquitination. Located in several cellular components, including early endosome; endoplasmic reticulum; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000261442 (HGNC:58541):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGRN1	NM_015246.4	MANE Select	c.88+9399G>C		intron	N/A	NP_056061.1
	MGRN1	NM_001142289.3		c.88+9399G>C		intron	N/A	NP_001135761.2
	MGRN1	NM_001142290.3		c.88+9399G>C		intron	N/A	NP_001135762.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGRN1	ENST00000262370.12	TSL:1 MANE Select	c.88+9399G>C		intron	N/A	ENSP00000262370.6
	MGRN1	ENST00000588994.5	TSL:1	c.88+9399G>C		intron	N/A	ENSP00000468819.1
	MGRN1	ENST00000399577.9	TSL:1	c.88+9399G>C		intron	N/A	ENSP00000382487.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.069
DANN	Benign	0.47
PhyloP100		-3.8

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: rs1659506; hg19: chr16-4684448;