3-108986519-T-C

Variant names:

• chr3-108986519-T-C
• rs2593963
• NM_014429.4:c.2257+361A>G

Variant summary

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

The NM_014429.4(MORC1):​c.2257+361A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,992 control chromosomes in the GnomAD database, including 14,119 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 0.42 (14119 hom., cov: 31)
• Consequence: MORC1 NM_014429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 2 publications found

Genes affected

MORC1 (HGNC:7198): (MORC family CW-type zinc finger 1) This gene encodes the human homolog of mouse morc and like the mouse protein it is testis-specific. Mouse studies support a testis-specific function since only male knockout mice are infertile; infertility is the only apparent defect. These studies further support a role for this protein early in spermatogenesis, possibly by affecting entry into apoptosis because testis from knockout mice show greatly increased numbers of apoptotic cells. [provided by RefSeq, Jan 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MORC1	NM_014429.4	c.2257+361A>G		intron_variant	Intron 22 of 27	ENST00000232603.10	NP_055244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MORC1	ENST00000232603.10	c.2257+361A>G		intron_variant	Intron 22 of 27	1	NM_014429.4	ENSP00000232603.5
MORC1	ENST00000483760.1	c.2194+361A>G		intron_variant	Intron 21 of 26	2		ENSP00000417282.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63830 AN: 151874 Hom.: 14092 Cov.: 31

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 63902 AN: 151992 Hom.: 14119 Cov.: 31 AF XY: 0.413 AC XY: 30648 AN XY: 74272

African (AFR) AF: 0.515 AC: 21338 AN: 41424

American (AMR) AF: 0.324 AC: 4943 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1836 AN: 3472

East Asian (EAS) AF: 0.0907 AC: 470 AN: 5180

South Asian (SAS) AF: 0.379 AC: 1823 AN: 4816

European-Finnish (FIN) AF: 0.340 AC: 3591 AN: 10554

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28431 AN: 67968

Other (OTH) AF: 0.453 AC: 959 AN: 2116

Alfa AF: 0.276 Hom.: 651

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.40
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: rs2593963; hg19: chr3-108705366;