Genetic Variant SHROOM4:p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln (chrX-50607758-C-CTGCTGCTGCTGTTGCTGCTGT) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

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: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_020717.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020717.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SHROOM4	NM_020717.5	MANE Select	c.3383_3384insACAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 6 of 9	NP_065768.2
SHROOM4	NR_027121.3		n.3559_3560insACAGCAGCAACAGCAGCAGCA		non_coding_transcript_exon	Exon 6 of 10
SHROOM4	NR_172068.1		n.3424_3425insACAGCAGCAACAGCAGCAGCA		non_coding_transcript_exon	Exon 5 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SHROOM4	ENST00000376020.9	TSL:2 MANE Select	c.3383_3384insACAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 6 of 9	ENSP00000365188.2
SHROOM4	ENST00000289292.11	TSL:1	c.3383_3384insACAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 6 of 10	ENSP00000289292.7
SHROOM4	ENST00000460112.3	TSL:5	c.3035_3036insACAGCAGCAACAGCAGCAGCA	p.Gln1012_Lys1013insGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	Exon 5 of 8	ENSP00000421450.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over