4-76741016-TG-TGGGG

Variant names:

• chr4-76741016-T-TGGG
• rs863225433
• NM_020859.4:c.2846_2848dupGGG

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_020859.4(SHROOM3):​c.2846_2848dupGGG​(p.Gly949dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,938 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: SHROOM3 NM_020859.4 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 0 publications found

Genes affected

SHROOM3 (HGNC:30422): (shroom family member 3) This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

SHROOM3-AS1 (HGNC:41265): (SHROOM3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_020859.4. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020859.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	NM_020859.4	MANE Select	c.2846_2848dupGGG	p.Gly949dup	disruptive_inframe_insertion	Exon 5 of 11	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.1044+1789_1044+1791dupCCC		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.500+1789_500+1791dupCCC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.2846_2848dupGGG	p.Gly949dup	disruptive_inframe_insertion	Exon 5 of 11	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.2849_2851dupGGG	p.Gly950dup	disruptive_inframe_insertion	Exon 5 of 11	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.2603_2605dupGGG	p.Gly868dup	disruptive_inframe_insertion	Exon 4 of 10	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000113 AC: 1 AN: 88746 AF XY: 0.0000215

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333938 Hom.: 0 Cov.: 80 AF XY: 0.00000153 AC XY: 1 AN XY: 652968

African (AFR) AF: 0.00 AC: 0 AN: 29114

American (AMR) AF: 0.00 AC: 0 AN: 23222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19864

East Asian (EAS) AF: 0.00 AC: 0 AN: 35592

South Asian (SAS) AF: 0.0000151 AC: 1 AN: 66144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45446

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1054104

Other (OTH) AF: 0.00 AC: 0 AN: 55084

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs863225433; hg19: chr4-77662169;