3-109084487-T-G

Position:

• chr3-109084487-T-G

Variant summary

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

The NM_014429.4(MORC1):​c.689+8949A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,110 control chromosomes in the GnomAD database, including 59,099 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 0.88 (59099 hom., cov: 32)
• Consequence: MORC1 NM_014429.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MORC1	NM_014429.4	c.689+8949A>C		intron_variant		ENST00000232603.10	NP_055244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MORC1	ENST00000232603.10	c.689+8949A>C		intron_variant		1	NM_014429.4	ENSP00000232603.5
MORC1	ENST00000483760.1	c.689+8949A>C		intron_variant		2		ENSP00000417282.1

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133890 AN: 151994 Hom.: 59048 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.877

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.859

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.881 AC: 133994 AN: 152110 Hom.: 59099 Cov.: 32 AF XY: 0.881 AC XY: 65553 AN XY: 74368

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.850

Gnomad4 EAS AF: 0.928

Gnomad4 SAS AF: 0.870

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.859

Gnomad4 OTH AF: 0.875

Alfa AF: 0.877 Hom.: 7269

Bravo AF: 0.884

Asia WGS AF: 0.878 AC: 3050 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.75

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: rs4507260; hg19: chr3-108803334;