X-17376088-TCGGCGGCGG-TCGGCGGCGGCGGCGGCGG

Position:

• chrX-17376088-TCGGCGGCGG-TCGGCGGCGGCGGCGGCGG

Variant summary

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

The NM_001291867.2(NHS):​c.342_350dupGGCGGCGGC​(p.Ala115_Ala117dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000835 in 1,078,392 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: 𝑓 0.0000091 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000083 (0 hom. 1 hem.)
• Consequence: NHS NM_001291867.2 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485

Genes affected

NHS (HGNC:7820): (NHS actin remodeling regulator) This gene encodes a protein containing four conserved nuclear localization signals. The encoded protein functions in eye, tooth, craniofacial and brain development, and it can regulate actin remodeling and cell morphology. Mutations in this gene have been shown to cause Nance-Horan syndrome, and also X-linked cataract-40. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHS	NM_001291867.2	c.342_350dupGGCGGCGGC	p.Ala115_Ala117dup	disruptive_inframe_insertion	1/9	ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.342_350dupGGCGGCGGC	p.Ala115_Ala117dup	disruptive_inframe_insertion	1/8		NP_938011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.342_350dupGGCGGCGGC	p.Ala115_Ala117dup	disruptive_inframe_insertion	1/9		NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.342_350dupGGCGGCGGC	p.Ala115_Ala117dup	disruptive_inframe_insertion	1/8	1		ENSP00000369400.3

Frequencies

GnomAD3 genomes AF: 0.00000906 AC: 1 AN: 110367 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33339

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: 0.0000191

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000826 AC: 8 AN: 968025 Hom.: 0 Cov.: 31 AF XY: 0.00000326 AC XY: 1 AN XY: 306971

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000254

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000763

Gnomad4 OTH exome AF: 0.0000246

GnomAD4 genome AF: 0.00000906 AC: 1 AN: 110367 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33339

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: 0.0000191

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000151

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: rs587780401; hg19: chrX-17394211;