X-50607758-C-CTGCTGCTGCTGTTGCTGCTGCTGTTGCTGCTTCTGCTGCTGCTGT

Position:

• chrX-50607758-C-CTGCTGCTGCTGTTGCTGCTGCTGTTGCTGCTTCTGCTGCTGCTGT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020717.5(SHROOM4):​c.3383_3384insACAGCAGCAGCAGAAGCAGCAACAGCAGCAGCAACAGCAGCAGCA​(p.Gln1128_Lys1129insGlnGlnGlnGlnLysGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000928 in 107,731 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000093 (0 hom., 0 hem., cov: 0)
• Consequence: SHROOM4 NM_020717.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.3383_3384insACAGCAGCAGCAGAAGCAGCAACAGCAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnLysGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	6/9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.3383_3384insACAGCAGCAGCAGAAGCAGCAACAGCAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnLysGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	6/9	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.3383_3384insACAGCAGCAGCAGAAGCAGCAACAGCAGCAGCAACAGCAGCAGCA	p.Gln1128_Lys1129insGlnGlnGlnGlnLysGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	6/10	1		ENSP00000289292.7
SHROOM4	ENST00000460112.3	c.3035_3036insACAGCAGCAGCAGAAGCAGCAACAGCAGCAGCAACAGCAGCAGCA	p.Gln1012_Lys1013insGlnGlnGlnGlnLysGlnGlnGlnGlnGlnGlnGlnGlnGlnGln	disruptive_inframe_insertion	5/8	5		ENSP00000421450.1

Frequencies

GnomAD3 genomes AF: 0.00000928 AC: 1 AN: 107731 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30363

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000192

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000928 AC: 1 AN: 107731 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30363

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000192

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201922875; hg19: chrX-50350758;