X-17375203-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001291867.2(NHS):c.-555G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 111,683 control chromosomes in the GnomAD database, including 28 homozygotes. There are 711 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.022 (28 hom., 711 hem., cov: 23)
• Consequence: NHS NM_001291867.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant X-17375203-G-A is Benign according to our data. Variant chrX-17375203-G-A is described in ClinVar as [Benign]. Clinvar id is 1275467.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0221 (2467/111683) while in subpopulation NFE AF= 0.0327 (1726/52860). AF 95% confidence interval is 0.0314. There are 28 homozygotes in gnomad4. There are 711 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NHS	NM_001291867.2	c.-555G>A		5_prime_UTR_variant	1/9	ENST00000676302.1
NHS	NM_198270.4	c.-555G>A		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NHS	ENST00000676302.1	c.-555G>A		5_prime_UTR_variant	1/9		NM_001291867.2	P4

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 2467 AN: 111636 Hom.: 28 Cov.: 23 AF XY: 0.0210 AC XY: 710 AN XY: 33856

Gnomad AFR AF: 0.00368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0363

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0169

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0207

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

GnomAD4 genome AF: 0.0221 AC: 2467 AN: 111683 Hom.: 28 Cov.: 23 AF XY: 0.0210 AC XY: 711 AN XY: 33913

Gnomad4 AFR AF: 0.00367

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.0363

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0119

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0277 Hom.: 152

Bravo AF: 0.0188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	16
Dann	Benign	0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62586064; hg19: chrX-17393326;