X-50607728-TTCCTCC-TTCCTCCTCCTCCTCC

Variant names:

• chrX-50607728-T-TTCCTCCTCC
• NM_020717.5:c.3405_3413dupGGAGGAGGA

Variant summary

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

The NM_020717.5(SHROOM4):​c.3405_3413dupGGAGGAGGA​(p.Glu1136_Glu1138dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000396 in 1,011,016 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.0000040 (0 hom. 1 hem.)
• Consequence: SHROOM4 NM_020717.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.350

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]

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 rank	MANE	Protein	UniProt
SHROOM4	NM_020717.5	c.3405_3413dupGGAGGAGGA	p.Glu1136_Glu1138dup	disruptive_inframe_insertion	Exon 6 of 9	ENST00000376020.9	NP_065768.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHROOM4	ENST00000376020.9	c.3405_3413dupGGAGGAGGA	p.Glu1136_Glu1138dup	disruptive_inframe_insertion	Exon 6 of 9	2	NM_020717.5	ENSP00000365188.2
SHROOM4	ENST00000289292.11	c.3405_3413dupGGAGGAGGA	p.Glu1136_Glu1138dup	disruptive_inframe_insertion	Exon 6 of 10	1		ENSP00000289292.7
SHROOM4	ENST00000460112.3	c.3057_3065dupGGAGGAGGA	p.Glu1020_Glu1022dup	disruptive_inframe_insertion	Exon 5 of 8	5		ENSP00000421450.1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome AF: 0.00000396 AC: 4 AN: 1011016 Hom.: 0 Cov.: 30 AF XY: 0.00000328 AC XY: 1 AN XY: 304960

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000103

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000234

GnomAD4 genome Cov.: 14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-50350728;