rs17253722

Variant names:

• chr4-76446134-G-A
• rs17253722
• NM_020859.4:c.168+9914G>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.168+9914G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,916 control chromosomes in the GnomAD database, including 9,187 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 0.32 (9187 hom., cov: 31)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 12 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.168+9914G>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.168+9914G>A		intron_variant	Intron 1 of 10	1	NM_020859.4	ENSP00000296043.6
SHROOM3	ENST00000466541.1	n.75+9914G>A		intron_variant	Intron 1 of 2	3
SHROOM3	ENST00000497440.5	n.109+9914G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49320 AN: 151798 Hom.: 9180 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.325 AC: 49358 AN: 151916 Hom.: 9187 Cov.: 31 AF XY: 0.319 AC XY: 23708 AN XY: 74238

African (AFR) AF: 0.167 AC: 6923 AN: 41454

American (AMR) AF: 0.345 AC: 5264 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1387 AN: 3468

East Asian (EAS) AF: 0.142 AC: 734 AN: 5166

South Asian (SAS) AF: 0.149 AC: 716 AN: 4814

European-Finnish (FIN) AF: 0.397 AC: 4175 AN: 10522

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29185 AN: 67904

Other (OTH) AF: 0.330 AC: 698 AN: 2114

Alfa AF: 0.301 Hom.: 2163

Bravo AF: 0.318

Asia WGS AF: 0.141 AC: 492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.9
DANN	Benign	0.42
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: rs17253722; hg19: chr4-77367287;