rs2197741

Positions:

• chr3-109013262-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014429.4(MORC1):​c.1705-6171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,120 control chromosomes in the GnomAD database, including 62,712 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 0.90 (62712 hom., cov: 31)
• Consequence: MORC1 NM_014429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORC1	NM_014429.4	c.1705-6171G>A		intron_variant		ENST00000232603.10	NP_055244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORC1	ENST00000232603.10	c.1705-6171G>A		intron_variant		1	NM_014429.4	ENSP00000232603.5
MORC1	ENST00000483760.1	c.1705-7947G>A		intron_variant		2		ENSP00000417282.1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136726 AN: 152002 Hom.: 62676 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.899 AC: 136815 AN: 152120 Hom.: 62712 Cov.: 31 AF XY: 0.902 AC XY: 67113 AN XY: 74388

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.948

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.914

Alfa AF: 0.935 Hom.: 9071

Bravo AF: 0.888

Asia WGS AF: 0.967 AC: 3362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.59
DANN	Benign	0.46

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: rs2197741; hg19: chr3-108732109;