NM_014429.4:c.689+8949A>C

Variant names:

• chr3-109084487-T-G
• rs4507260
• NM_014429.4:c.689+8949A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014429.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC1	NM_014429.4	MANE Select	c.689+8949A>C		intron	N/A	NP_055244.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MORC1	ENST00000232603.10	TSL:1 MANE Select	c.689+8949A>C		intron	N/A	ENSP00000232603.5
	MORC1	ENST00000483760.1	TSL:2	c.689+8949A>C		intron	N/A	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

African (AFR) AF: 0.903 AC: 37490 AN: 41524

American (AMR) AF: 0.907 AC: 13865 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2947 AN: 3466

East Asian (EAS) AF: 0.928 AC: 4807 AN: 5182

South Asian (SAS) AF: 0.870 AC: 4190 AN: 4814

European-Finnish (FIN) AF: 0.891 AC: 9421 AN: 10576

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.859 AC: 58366 AN: 67954

Other (OTH) AF: 0.875 AC: 1844 AN: 2108

Alfa AF: 0.878 Hom.: 7578

Bravo AF: 0.884

Asia WGS AF: 0.878 AC: 3050 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.75
PhyloP100		-2.1
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: rs4507260; hg19: chr3-108803334;