4-76537426-A-G

Variant names:

• chr4-76537426-A-G
• rs4256249
• NM_020859.4:c.169-18183A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020859.4(SHROOM3):​c.169-18183A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,902 control chromosomes in the GnomAD database, including 34,791 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 0.67 (34791 hom., cov: 30)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 4 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 Gene-Disease associations (from GenCC):

• neural tube defect

  Inheritance: AD Classification: STRONG Submitted by: G2P
• syndromic disease

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

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.169-18183A>G		intron	N/A	NP_065910.3	Q8TF72-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHROOM3	ENST00000296043.7	TSL:1 MANE Select	c.169-18183A>G		intron	N/A	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.169-18180A>G		intron	N/A	ENSP00000582825.1
	SHROOM3	ENST00000466541.1	TSL:3	n.76-18183A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102162 AN: 151784 Hom.: 34768 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.831

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.673 AC: 102233 AN: 151902 Hom.: 34791 Cov.: 30 AF XY: 0.679 AC XY: 50400 AN XY: 74232

African (AFR) AF: 0.662 AC: 27384 AN: 41382

American (AMR) AF: 0.753 AC: 11503 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3470

East Asian (EAS) AF: 0.942 AC: 4857 AN: 5158

South Asian (SAS) AF: 0.832 AC: 4002 AN: 4808

European-Finnish (FIN) AF: 0.658 AC: 6935 AN: 10542

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43263 AN: 67940

Other (OTH) AF: 0.682 AC: 1442 AN: 2114

Alfa AF: 0.661 Hom.: 18544

Bravo AF: 0.678

Asia WGS AF: 0.862 AC: 2998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.69
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: rs4256249; hg19: chr4-77458579;