Genetic Variant MORC3:c.1406+507T>C (chr21-36360765-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.26

Publications

1 publications found

Variant links:

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]

MORC3 links:

ENSG00000228107 (HGNC:):

ENSG00000228107 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111694

AN:

151934

Hom.:

42182

Cov.:

show subpopulations

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.:

AF XY:

0.677

AC XY:

2674

AN XY:

3948

show subpopulations

African (AFR)

AF:

0.881

AC:

AN:

American (AMR)

AF:

0.795

AC:

1084

AN:

1364

Ashkenazi Jewish (ASJ)

AF:

0.667

AC:

AN:

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:

AN:

130

Middle Eastern (MID)

AF:

0.786

AC:

AN:

European-Non Finnish (NFE)

AF:

0.583

AC:

2657

AN:

4554

Other (OTH)

AF:

0.599

AC:

181

AN:

302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

140

209

279

349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.735

AC:

111817

AN:

152052

Hom.:

42244

Cov.:

AF XY:

0.742

AC XY:

55168

AN XY:

74332

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1436

2872

4308

5744

7180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.77

(source)

DANN

Benign

0.58

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over