NM_015358.3:c.1406+507T>C

Variant names:

• chr21-36360765-T-C
• rs2835340
• NM_015358.3:c.1406+507T>C

Variant summary

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

The NM_015358.3(MORC3):​c.1406+507T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 159,540 control chromosomes in the GnomAD database, including 44,018 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 0.74 (42244 hom., cov: 31)
  • Exomes 𝑓: 0.67 (1774 hom.)
• Consequence: MORC3 NM_015358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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]

ENSG00000228107 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015358.3. 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
	MORC3	NM_015358.3	MANE Select	c.1406+507T>C		intron	N/A	NP_056173.1
	MORC3	NM_001320445.2		c.1193+507T>C		intron	N/A	NP_001307374.1
	MORC3	NM_001320446.2		c.1193+507T>C		intron	N/A	NP_001307375.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC3	ENST00000400485.6	TSL:1 MANE Select	c.1406+507T>C		intron	N/A	ENSP00000383333.1
	ENSG00000228107	ENST00000397184.2	TSL:5	n.136T>C		non_coding_transcript_exon	Exon 1 of 2
	MORC3	ENST00000487909.5	TSL:2	n.1367+507T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111694 AN: 151934 Hom.: 42182 Cov.: 31

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.668 AC: 5004 AN: 7488 Hom.: 1774 Cov.: 0 AF XY: 0.677 AC XY: 2674 AN XY: 3948

African (AFR) AF: 0.881 AC: 37 AN: 42

American (AMR) AF: 0.795 AC: 1084 AN: 1364

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 40 AN: 60

East Asian (EAS) AF: 1.00 AC: 256 AN: 256

South Asian (SAS) AF: 0.856 AC: 656 AN: 766

European-Finnish (FIN) AF: 0.631 AC: 82 AN: 130

Middle Eastern (MID) AF: 0.786 AC: 11 AN: 14

European-Non Finnish (NFE) AF: 0.583 AC: 2657 AN: 4554

Other (OTH) AF: 0.599 AC: 181 AN: 302

GnomAD4 genome AF: 0.735 AC: 111817 AN: 152052 Hom.: 42244 Cov.: 31 AF XY: 0.742 AC XY: 55168 AN XY: 74332

African (AFR) AF: 0.868 AC: 36038 AN: 41500

American (AMR) AF: 0.761 AC: 11608 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2459 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5171 AN: 5186

South Asian (SAS) AF: 0.888 AC: 4282 AN: 4824

European-Finnish (FIN) AF: 0.695 AC: 7348 AN: 10566

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42582 AN: 67946

Other (OTH) AF: 0.726 AC: 1528 AN: 2106

Alfa AF: 0.669 Hom.: 17670

Bravo AF: 0.745

Asia WGS AF: 0.940 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
DANN	Benign	0.58
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs2835340; hg19: chr21-37733063;