rs4859682

Variant names:

• chr4-76489165-C-A
• rs4859682
• NM_020859.4:c.168+52945C>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+52945C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,102 control chromosomes in the GnomAD database, including 9,664 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 0.33 (9664 hom., cov: 32)
• Consequence: SHROOM3 NM_020859.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.689
• Publications: 23 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM3	NM_020859.4	c.168+52945C>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+52945C>A		intron_variant	Intron 1 of 10	1	NM_020859.4	ENSP00000296043.6
SHROOM3	ENST00000466541.1	n.75+52945C>A		intron_variant	Intron 1 of 2	3
SHROOM3	ENST00000497440.5	n.109+52945C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49725 AN: 151984 Hom.: 9660 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.327 AC: 49736 AN: 152102 Hom.: 9664 Cov.: 32 AF XY: 0.323 AC XY: 23984 AN XY: 74360

African (AFR) AF: 0.130 AC: 5378 AN: 41496

American (AMR) AF: 0.345 AC: 5275 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1158 AN: 5160

South Asian (SAS) AF: 0.161 AC: 774 AN: 4818

European-Finnish (FIN) AF: 0.427 AC: 4515 AN: 10580

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

European-Non Finnish (NFE) AF: 0.445 AC: 30260 AN: 67978

Other (OTH) AF: 0.328 AC: 692 AN: 2112

Alfa AF: 0.408 Hom.: 57650

Bravo AF: 0.317

Asia WGS AF: 0.181 AC: 631 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.61
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: rs4859682; hg19: chr4-77410318;