rs2835340

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr21-36360765-T-A
• chr21-36360765-T-C

Variant summary

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

The NM_015358.3(MORC3):​c.1406+507T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 7,506 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: MORC3 NM_015358.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 0 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: 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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORC3	NM_015358.3	c.1406+507T>A		intron_variant	Intron 12 of 16	ENST00000400485.6	NP_056173.1
MORC3	NM_001320445.2	c.1193+507T>A		intron_variant	Intron 11 of 15		NP_001307374.1
MORC3	NM_001320446.2	c.1193+507T>A		intron_variant	Intron 13 of 17		NP_001307375.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORC3	ENST00000400485.6	c.1406+507T>A		intron_variant	Intron 12 of 16	1	NM_015358.3	ENSP00000383333.1
ENSG00000228107	ENST00000397184.2	n.136T>A		non_coding_transcript_exon_variant	Exon 1 of 2	5
MORC3	ENST00000487909.5	n.1367+507T>A		intron_variant	Intron 11 of 15	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.000133 AC: 1 AN: 7506 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3964

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 42

American (AMR) AF: 0.00 AC: 0 AN: 1366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 60

East Asian (EAS) AF: 0.00 AC: 0 AN: 256

South Asian (SAS) AF: 0.00 AC: 0 AN: 768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.000219 AC: 1 AN: 4566

Other (OTH) AF: 0.00 AC: 0 AN: 304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.66
DANN	Benign	0.60
PhyloP100		-1.3

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;