21-36362212-C-G

Variant names:

• chr21-36362212-C-G
• rs541408590
• NM_015358.3:c.1436C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015358.3(MORC3):​c.1436C>G​(p.Pro479Arg) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P479L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MORC3 NM_015358.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07673141).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC3	NM_015358.3	MANE Select	c.1436C>G	p.Pro479Arg	missense	Exon 13 of 17	NP_056173.1	Q14149
	MORC3	NM_001320445.2		c.1223C>G	p.Pro408Arg	missense	Exon 12 of 16	NP_001307374.1	B4DHJ4
	MORC3	NM_001320446.2		c.1223C>G	p.Pro408Arg	missense	Exon 14 of 18	NP_001307375.1	B4DHJ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC3	ENST00000400485.6	TSL:1 MANE Select	c.1436C>G	p.Pro479Arg	missense	Exon 13 of 17	ENSP00000383333.1	Q14149
	MORC3	ENST00000484028.1	TSL:3	n.377C>G		non_coding_transcript_exon	Exon 1 of 3
	MORC3	ENST00000487909.5	TSL:2	n.1397C>G		non_coding_transcript_exon	Exon 12 of 16

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.9
DANN	Benign	0.80
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.028
Sift	Benign	0.030	D
Sift4G	Benign	0.52	T
Polyphen		0.53	P
Vest4		0.21
MutPred		0.24		Gain of MoRF binding (P = 0.0069)
MVP		0.11
MPC		0.20
ClinPred		0.27	T
GERP RS		0.27
Varity_R		0.056
gMVP		0.30
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs541408590; hg19: chr21-37734510;