rs13106227

Variant names:

• chr4-76497528-G-A
• rs13106227
• NM_020859.4:c.169-58081G>A

Variant summary

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

The NM_020859.4(SHROOM3):​c.169-58081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,012 control chromosomes in the GnomAD database, including 25,616 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 0.57 (25616 hom., cov: 33)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 20 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.169-58081G>A		intron_variant	Intron 1 of 10	ENST00000296043.7	NP_065910.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM3	ENST00000296043.7	c.169-58081G>A		intron_variant	Intron 1 of 10	1	NM_020859.4	ENSP00000296043.6
SHROOM3	ENST00000466541.1	n.76-58081G>A		intron_variant	Intron 1 of 2	3
SHROOM3	ENST00000497440.5	n.110-58081G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86714 AN: 151894 Hom.: 25607 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.598

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

GnomAD4 genome AF: 0.571 AC: 86757 AN: 152012 Hom.: 25616 Cov.: 33 AF XY: 0.569 AC XY: 42296 AN XY: 74300

African (AFR) AF: 0.426 AC: 17659 AN: 41478

American (AMR) AF: 0.610 AC: 9309 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2288 AN: 3462

East Asian (EAS) AF: 0.533 AC: 2761 AN: 5176

South Asian (SAS) AF: 0.607 AC: 2930 AN: 4828

European-Finnish (FIN) AF: 0.607 AC: 6399 AN: 10546

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43630 AN: 67936

Other (OTH) AF: 0.593 AC: 1249 AN: 2108

Alfa AF: 0.621 Hom.: 89985

Bravo AF: 0.566

Asia WGS AF: 0.523 AC: 1823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.52
PhyloP100		1.2
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: rs13106227; hg19: chr4-77418681;