Genetic Variant SHROOM4:p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln (chrX-50607758-C-CTGCTGCTGCTGTTGCTGCTGT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_020717.5(SHROOM4):c.3383_3384insACAGCAGCAACAGCAGCAGCA(p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q1128Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0000046 ( 0 hom. 5 hem. )

Failed GnomAD Quality Control

Consequence

SHROOM4
NM_020717.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.676

Publications

11 publications found

Variant links:

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

SHROOM4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5 link	c.3383_3384insACAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 6 of 9	ENST00000376020.9	NP_065768.2	Q9ULL8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SHROOM4	ENST00000376020.9 link	c.3383_3384insACAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 6 of 9	2	NM_020717.5	ENSP00000365188.2	Q9ULL8-1
SHROOM4	ENST00000289292.11 link	c.3383_3384insACAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 6 of 10	1		ENSP00000289292.7	Q9ULL8-1
SHROOM4	ENST00000460112.3 link	c.3035_3036insACAGCAGCAACAGCAGCAGCA	p.Gln1012_Lys1013insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 5 of 8	5		ENSP00000421450.1	Q9ULL8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

165426

AF XY:

0.0000361

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000279

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000459

AC:

AN:

1089626

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

356438

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26240

American (AMR)

AF:

0.00

AC:

AN:

34946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19169

East Asian (EAS)

AF:

0.00

AC:

AN:

30117

South Asian (SAS)

AF:

0.00

AC:

AN:

53350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40250

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4061

European-Non Finnish (NFE)

AF:

0.00000598

AC:

AN:

835737

Other (OTH)

AF:

0.00

AC:

AN:

45756

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000790

Hom.:

3030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.68

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over