chrX-17375203-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 28 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NHSNM_001291867.2 linkuse as main transcriptc.-555G>A 5_prime_UTR_variant 1/9 ENST00000676302.1
NHSNM_198270.4 linkuse as main transcriptc.-555G>A 5_prime_UTR_variant 1/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NHSENST00000676302.1 linkuse as main transcriptc.-555G>A 5_prime_UTR_variant 1/9 NM_001291867.2 P4Q6T4R5-1

Frequencies

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxSep 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62586064; hg19: chrX-17393326; API