rs2382659

Variant names:

• chrX-50785333-T-A
• rs2382659
• NM_020717.5:c.117+28569A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-50785333-T-A
• chrX-50785333-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020717.5(SHROOM4):​c.117+28569A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.78 (26795 hom., 25928 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: SHROOM4 NM_020717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.764
• Publications: 0 publications found

Genes affected

SHROOM4 (HGNC:29215): (shroom family member 4) This gene encodes a member of the APX/Shroom family, which contain an N-terminal PDZ domain and a C-terminal ASD2 motif. The encoded protein may play a role in cytoskeletal architecture. Mutations in this gene have been linked to the X-linked Stocco dos Santos syndrome characterized by cognitive disabilities. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2017]

SHROOM4 Gene-Disease associations (from GenCC):

• X-linked intellectual disability, Stocco dos Santos type

  Inheritance: XL Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• complex neurodevelopmental disorder

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics
• X-linked complex neurodevelopmental disorder

  Inheritance: XL Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.117+28569A>T		intron_variant	Intron 1 of 8	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.117+28569A>T		intron_variant	Intron 1 of 8	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.117+28569A>T		intron_variant	Intron 1 of 9	1		ENSP00000289292.7

Frequencies

GnomAD3 genomes AF: 0.782 AC: 86312 AN: 110377 Hom.: 26808 Cov.: 23

Gnomad AFR AF: 0.314

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.988

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.820

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.782 AC: 86303 AN: 110429 Hom.: 26795 Cov.: 23 AF XY: 0.792 AC XY: 25928 AN XY: 32731

African (AFR) AF: 0.313 AC: 9551 AN: 30496

American (AMR) AF: 0.906 AC: 9338 AN: 10306

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 2361 AN: 2635

East Asian (EAS) AF: 0.992 AC: 3468 AN: 3497

South Asian (SAS) AF: 0.957 AC: 2430 AN: 2539

European-Finnish (FIN) AF: 0.988 AC: 5703 AN: 5771

Middle Eastern (MID) AF: 0.883 AC: 189 AN: 214

European-Non Finnish (NFE) AF: 0.973 AC: 51329 AN: 52767

Other (OTH) AF: 0.822 AC: 1246 AN: 1516

Alfa AF: 0.822 Hom.: 5504

Bravo AF: 0.756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		0.76
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: rs2382659; hg19: chrX-50528333;