chrX-17375877-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001291867.2(NHS):​c.120G>T​(p.Pro40Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000001 in 995,842 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000010 ( 0 hom. 0 hem. )

Consequence

NHS
NM_001291867.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.928
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant X-17375877-G-T is Benign according to our data. Variant chrX-17375877-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1995455.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.928 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NHSNM_001291867.2 linkc.120G>T p.Pro40Pro synonymous_variant Exon 1 of 9 ENST00000676302.1 NP_001278796.1 Q6T4R5-1
NHSNM_198270.4 linkc.120G>T p.Pro40Pro synonymous_variant Exon 1 of 8 NP_938011.1 Q6T4R5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NHSENST00000676302.1 linkc.120G>T p.Pro40Pro synonymous_variant Exon 1 of 9 NM_001291867.2 ENSP00000502262.1 Q6T4R5-1
NHSENST00000380060.7 linkc.120G>T p.Pro40Pro synonymous_variant Exon 1 of 8 1 ENSP00000369400.3 Q6T4R5-2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000100
AC:
1
AN:
995842
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
320532
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000125
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Nance-Horan syndrome Benign:1
May 20, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
6.9
DANN
Benign
0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-17394000; API