rs10521675

chrX-17592737-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001291867.2(NHS):c.566-95005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00697 in 111,847 control chromosomes in the GnomAD database, including 6 homozygotes. There are 226 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0070 (6 hom., 226 hem., cov: 22)
• Consequence: NHS NM_001291867.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00697 (780/111847) while in subpopulation SAS AF= 0.0247 (66/2676). AF 95% confidence interval is 0.0199. There are 6 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHS	NM_001291867.2	c.566-95005T>C		intron_variant		ENST00000676302.1
NHS	NM_198270.4	c.566-95005T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHS	ENST00000676302.1	c.566-95005T>C		intron_variant			NM_001291867.2	P4
NHS	ENST00000380060.7	c.566-95005T>C		intron_variant		1		A2

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 779 AN: 111796 Hom.: 6 Cov.: 22 AF XY: 0.00665 AC XY: 226 AN XY: 33982

Gnomad AFR AF: 0.00107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00456

Gnomad ASJ AF: 0.0348

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.00298

Gnomad MID AF: 0.0546

Gnomad NFE AF: 0.00921

Gnomad OTH AF: 0.0133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00697 AC: 780 AN: 111847 Hom.: 6 Cov.: 22 AF XY: 0.00664 AC XY: 226 AN XY: 34043

Gnomad4 AFR AF: 0.00107

Gnomad4 AMR AF: 0.00456

Gnomad4 ASJ AF: 0.0348

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.00298

Gnomad4 NFE AF: 0.00922

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.00855 Hom.: 54

Bravo AF: 0.00633

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521675; hg19: chrX-17610858;