chr4-76436338-C-CT

Variant names:

• chr4-76436338-C-CT
• rs200881265
• NM_020859.4:c.168+118_168+119insT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020859.4(SHROOM3):​c.168+118_168+119insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,127,024 control chromosomes in the GnomAD database, including 13,732 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (1915 hom., cov: 32)
  • Exomes 𝑓: 0.15 (11817 hom.)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328
• 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 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 -10 ACMG points.

• BP6: Variant 4-76436338-C-CT is Benign according to our data. Variant chr4-76436338-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1289955.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 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.168+118_168+119insT		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.168+118_168+119insT		intron	N/A	ENSP00000296043.6	Q8TF72-1
	SHROOM3	ENST00000912766.1		c.168+118_168+119insT		intron	N/A	ENSP00000582825.1
	SHROOM3	ENST00000466541.1	TSL:3	n.75+118_75+119insT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23955 AN: 151908 Hom.: 1911 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.149 AC: 145187 AN: 974998 Hom.: 11817 AF XY: 0.152 AC XY: 76155 AN XY: 500006

African (AFR) AF: 0.150 AC: 3454 AN: 22986

American (AMR) AF: 0.0715 AC: 2529 AN: 35376

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 3617 AN: 21054

East Asian (EAS) AF: 0.162 AC: 5874 AN: 36364

South Asian (SAS) AF: 0.222 AC: 15000 AN: 67642

European-Finnish (FIN) AF: 0.182 AC: 8231 AN: 45242

Middle Eastern (MID) AF: 0.151 AC: 466 AN: 3090

European-Non Finnish (NFE) AF: 0.142 AC: 99199 AN: 699484

Other (OTH) AF: 0.156 AC: 6817 AN: 43760

GnomAD4 genome AF: 0.158 AC: 23962 AN: 152026 Hom.: 1915 Cov.: 32 AF XY: 0.158 AC XY: 11702 AN XY: 74288

African (AFR) AF: 0.152 AC: 6316 AN: 41456

American (AMR) AF: 0.105 AC: 1605 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.200 AC: 1038 AN: 5188

South Asian (SAS) AF: 0.234 AC: 1131 AN: 4824

European-Finnish (FIN) AF: 0.196 AC: 2068 AN: 10550

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10645 AN: 67952

Other (OTH) AF: 0.170 AC: 358 AN: 2110

Alfa AF: 0.0480 Hom.: 71

Asia WGS AF: 0.206 AC: 718 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
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: rs200881265; hg19: chr4-77357491;