rs2835340

chr21-36360765-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MORC3	NM_015358.3	c.1406+507T>C		intron_variant		ENST00000400485.6
MORC3	NM_001320445.2	c.1193+507T>C		intron_variant
MORC3	NM_001320446.2	c.1193+507T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MORC3	ENST00000400485.6	c.1406+507T>C		intron_variant		1	NM_015358.3	P1
	ENST00000397184.2	n.136T>C		non_coding_transcript_exon_variant	1/2	5
MORC3	ENST00000487909.5	n.1367+507T>C		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.795

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.856

Gnomad4 FIN exome AF: 0.631

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.599

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

Gnomad4 AFR AF: 0.868

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.726

Alfa AF: 0.669 Hom.: 15752

Bravo AF: 0.745

Asia WGS AF: 0.940 AC: 3267 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.77
Dann	Benign	0.58

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: rs2835340; hg19: chr21-37733063;