rs17319721

Variant names:

• chr4-76447694-G-A
• rs17319721
• NM_020859.4:c.168+11474G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020859.4(SHROOM3):​c.168+11474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 152,018 control chromosomes in the GnomAD database, including 9,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9607 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.270
• Publications: 99 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 4-76447694-G-A is Benign according to our data. Variant chr4-76447694-G-A is described in ClinVar as Benign. ClinVar VariationId is 1263431.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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+11474G>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+11474G>A		intron_variant	Intron 1 of 10	1	NM_020859.4	ENSP00000296043.6
SHROOM3	ENST00000466541.1	n.75+11474G>A		intron_variant	Intron 1 of 2	3
SHROOM3	ENST00000497440.5	n.109+11474G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51298 AN: 151900 Hom.: 9606 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0974

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.338 AC: 51316 AN: 152018 Hom.: 9607 Cov.: 32 AF XY: 0.331 AC XY: 24615 AN XY: 74284

African (AFR) AF: 0.217 AC: 9010 AN: 41474

American (AMR) AF: 0.350 AC: 5337 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.0980 AC: 508 AN: 5184

South Asian (SAS) AF: 0.142 AC: 685 AN: 4822

European-Finnish (FIN) AF: 0.398 AC: 4192 AN: 10544

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29201 AN: 67938

Other (OTH) AF: 0.340 AC: 718 AN: 2114

Alfa AF: 0.395 Hom.: 40583

Bravo AF: 0.333

Asia WGS AF: 0.120 AC: 420 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23586973, 29476007, 25437874) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		0.27
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: rs17319721; hg19: chr4-77368847;