rs398124610

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_001291867.2(NHS):ā€‹c.513C>Gā€‹(p.Leu171Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000636 in 1,164,143 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 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: š‘“ 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes š‘“: 0.000068 ( 0 hom. 31 hem. )

Consequence

NHS
NM_001291867.2 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610
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 Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP7
Synonymous conserved (PhyloP=-0.061 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 31 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NHSNM_001291867.2 linkuse as main transcriptc.513C>G p.Leu171Leu synonymous_variant 1/9 ENST00000676302.1 NP_001278796.1 Q6T4R5-1
NHSNM_198270.4 linkuse as main transcriptc.513C>G p.Leu171Leu synonymous_variant 1/8 NP_938011.1 Q6T4R5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NHSENST00000676302.1 linkuse as main transcriptc.513C>G p.Leu171Leu synonymous_variant 1/9 NM_001291867.2 ENSP00000502262.1 Q6T4R5-1
NHSENST00000380060.7 linkuse as main transcriptc.513C>G p.Leu171Leu synonymous_variant 1/81 ENSP00000369400.3 Q6T4R5-2

Frequencies

GnomAD3 genomes
AF:
0.0000179
AC:
2
AN:
112043
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34251
show subpopulations
Gnomad AFR
AF:
0.0000324
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000189
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000378
AC:
4
AN:
105748
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
34738
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000722
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000684
AC:
72
AN:
1052100
Hom.:
0
Cov.:
32
AF XY:
0.0000907
AC XY:
31
AN XY:
341730
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:
0.0000382
Gnomad4 NFE exome
AF:
0.0000801
Gnomad4 OTH exome
AF:
0.000112
GnomAD4 genome
AF:
0.0000179
AC:
2
AN:
112043
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34251
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000189
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.52
CADD
Benign
8.1
DANN
Benign
0.88

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

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

Other links and lift over

dbSNP: rs398124610; hg19: chrX-17394393; API