chr21-36381734-G-A

Variant names:

• chr21-36381734-G-A
• rs218626
• ENST00000546482.5:n.*101-285G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000546482.5(MORC3):​n.*101-285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,824 control chromosomes in the GnomAD database, including 15,699 homozygotes. 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: 𝑓 0.44 (15699 hom., cov: 30)
• Consequence: MORC3 ENST00000546482.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 1 publications found

Genes affected

MORC3 (HGNC:23572): (MORC family CW-type zinc finger 3) This gene encodes a protein that localizes to the nuclear matrix and forms nuclear bodies via an ATP-dependent mechanism. The protein is predicted to have coiled-coil and zinc finger domains and has RNA binding activity. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000546482.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC3	ENST00000546482.5	TSL:2	n.*101-285G>A		intron	N/A	ENSP00000449467.1
	MORC3	ENST00000547657.1	TSL:2	n.425-285G>A		intron	N/A
	MORC3	ENST00000549948.5	TSL:2	n.*167+1052G>A		intron	N/A	ENSP00000447562.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66164 AN: 151706 Hom.: 15689 Cov.: 30

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.436 AC: 66206 AN: 151824 Hom.: 15699 Cov.: 30 AF XY: 0.424 AC XY: 31433 AN XY: 74162

African (AFR) AF: 0.575 AC: 23778 AN: 41384

American (AMR) AF: 0.375 AC: 5716 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1394 AN: 3462

East Asian (EAS) AF: 0.00561 AC: 29 AN: 5166

South Asian (SAS) AF: 0.144 AC: 694 AN: 4808

European-Finnish (FIN) AF: 0.343 AC: 3612 AN: 10522

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29557 AN: 67926

Other (OTH) AF: 0.429 AC: 903 AN: 2104

Alfa AF: 0.395 Hom.: 6059

Bravo AF: 0.445

Asia WGS AF: 0.110 AC: 386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	8.8
DANN	Benign	0.40
PhyloP100		-0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs218626; hg19: chr21-37754032;