X-17578848-G-T

Position:

• chrX-17578848-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001291867.2(NHS):​c.566-108894G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 111,329 control chromosomes in the GnomAD database, including 5,907 homozygotes. There are 6,771 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 0.22 (5907 hom., 6771 hem., cov: 23)
• Consequence: NHS NM_001291867.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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]

ENSG00000235834 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NHS	NM_001291867.2	c.566-108894G>T		intron_variant		ENST00000676302.1	NP_001278796.1
NHS	NM_198270.4	c.566-108894G>T		intron_variant			NP_938011.1
LOC101928389	NR_135631.1	n.325-7083G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NHS	ENST00000676302.1	c.566-108894G>T		intron_variant			NM_001291867.2	ENSP00000502262.1
NHS	ENST00000380060.7	c.566-108894G>T		intron_variant		1		ENSP00000369400.3
ENSG00000235834	ENST00000433228.1	n.325-7083G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.219 AC: 24326 AN: 111271 Hom.: 5899 Cov.: 23 AF XY: 0.201 AC XY: 6718 AN XY: 33495

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0390

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0763

Gnomad NFE AF: 0.00489

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.219 AC: 24407 AN: 111329 Hom.: 5907 Cov.: 23 AF XY: 0.202 AC XY: 6771 AN XY: 33563

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.0385

Gnomad4 SAS AF: 0.0818

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00489

Gnomad4 OTH AF: 0.194

Alfa AF: 0.204 Hom.: 1852

Bravo AF: 0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.012
DANN	Benign	0.48

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: rs6527811; hg19: chrX-17596969;