GeneBe

rs3747295

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001291867.2(NHS):​c.4018T>A​(p.Phe1340Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1340L) has been classified as Benign.

Frequency

Genomes: not found (cov: 22)

Consequence

NHS
NM_001291867.2 missense

Scores

15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.101

Publications

20 publications found
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]
NHS Gene-Disease associations (from GenCC):
  • Nance-Horan syndrome
    Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Ambry Genetics
  • early-onset nuclear cataract
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06153792).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291867.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NHS
NM_001291867.2
MANE Select
c.4018T>Ap.Phe1340Ile
missense
Exon 7 of 9NP_001278796.1Q6T4R5-1
NHS
NM_198270.4
c.3955T>Ap.Phe1319Ile
missense
Exon 6 of 8NP_938011.1Q6T4R5-2
NHS
NM_001440780.1
c.3679T>Ap.Phe1227Ile
missense
Exon 7 of 9NP_001427709.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
NHS
ENST00000676302.1
MANE Select
c.4018T>Ap.Phe1340Ile
missense
Exon 7 of 9ENSP00000502262.1Q6T4R5-1
NHS
ENST00000380060.7
TSL:1
c.3955T>Ap.Phe1319Ile
missense
Exon 6 of 8ENSP00000369400.3Q6T4R5-2
NHS
ENST00000398097.7
TSL:1
c.3487T>Ap.Phe1163Ile
missense
Exon 7 of 9ENSP00000381170.3Q6T4R5-3

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.050
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.90
CADD
Benign
5.1
DANN
Benign
0.88
DEOGEN2
Benign
0.0066
T
FATHMM_MKL
Benign
0.080
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.062
T
MetaSVM
Benign
-1.0
T
PhyloP100
0.10
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.69
N
REVEL
Benign
0.015
Sift
Benign
0.22
T
Sift4G
Benign
0.39
T
Vest4
0.16
MVP
0.13
MPC
0.49
ClinPred
0.040
T
GERP RS
0.69
gMVP
0.16
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs3747295; hg19: chrX-17746244; API