4-76754772-GA-TG

Variant names:

• chr4-76754772-GA-TG
• NM_020859.4:c.4289_4290delGAinsTG
• SHROOM3 p.Arg1430Leu

Variant summary

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

The NM_020859.4(SHROOM3):​c.4289_4290delGAinsTG​(p.Arg1430Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1430Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SHROOM3 NM_020859.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799
• 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 0 ACMG points.

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.4289_4290delGAinsTG	p.Arg1430Leu	missense	N/A	NP_065910.3	Q8TF72-1
	SHROOM3-AS1	NR_187404.1		n.951+3276_951+3277delTCinsCA		intron	N/A
	SHROOM3-AS1	NR_187405.1		n.408-11873_408-11872delTCinsCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.4289_4290delGAinsTG	p.Arg1430Leu	missense	N/A	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.4292_4293delGAinsTG	p.Arg1431Leu	missense	N/A	ENSP00000582825.1
	SHROOM3	ENST00000646790.1		c.4046_4047delGAinsTG	p.Arg1349Leu	missense	N/A	ENSP00000494970.1	A0A2R8Y5P9

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.80

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-77675925;