X-81115003-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_030763.3(HMGN5):​c.495G>C​(p.Glu165Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00037 in 1,148,328 control chromosomes in the GnomAD database, including 1 homozygotes. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., 55 hem., cov: 22)
Exomes 𝑓: 0.00021 ( 1 hom. 72 hem. )

Consequence

HMGN5
NM_030763.3 missense

Scores

17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.25
Variant links:
Genes affected
HMGN5 (HGNC:8013): (high mobility group nucleosome binding domain 5) This gene encodes a nuclear protein with similarities to the high mobility group proteins, HMG14 and HMG17, which suggests that this protein may function as a nucleosomal binding and transcriptional activating protein. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0047929585).
BP6
Variant X-81115003-C-G is Benign according to our data. Variant chrX-81115003-C-G is described in ClinVar as [Benign]. Clinvar id is 734671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAd4 at 55 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HMGN5NM_030763.3 linkc.495G>C p.Glu165Asp missense_variant Exon 7 of 7 ENST00000358130.7 NP_110390.1 P82970

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HMGN5ENST00000358130.7 linkc.495G>C p.Glu165Asp missense_variant Exon 7 of 7 2 NM_030763.3 ENSP00000350848.2 P82970

Frequencies

GnomAD3 genomes
AF:
0.00194
AC:
211
AN:
108889
Hom.:
0
Cov.:
22
AF XY:
0.00175
AC XY:
55
AN XY:
31509
show subpopulations
Gnomad AFR
AF:
0.00677
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000396
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00855
Gnomad NFE
AF:
0.0000191
Gnomad OTH
AF:
0.000695
GnomAD3 exomes
AF:
0.000450
AC:
46
AN:
102175
Hom.:
0
AF XY:
0.000311
AC XY:
10
AN XY:
32139
show subpopulations
Gnomad AFR exome
AF:
0.00521
Gnomad AMR exome
AF:
0.000351
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000513
Gnomad OTH exome
AF:
0.000682
GnomAD4 exome
AF:
0.000206
AC:
214
AN:
1039386
Hom.:
1
Cov.:
31
AF XY:
0.000215
AC XY:
72
AN XY:
335574
show subpopulations
Gnomad4 AFR exome
AF:
0.00655
Gnomad4 AMR exome
AF:
0.000466
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000217
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000981
Gnomad4 OTH exome
AF:
0.000664
GnomAD4 genome
AF:
0.00194
AC:
211
AN:
108942
Hom.:
0
Cov.:
22
AF XY:
0.00174
AC XY:
55
AN XY:
31570
show subpopulations
Gnomad4 AFR
AF:
0.00676
Gnomad4 AMR
AF:
0.000396
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000191
Gnomad4 OTH
AF:
0.000686
Alfa
AF:
0.000452
Hom.:
8
Bravo
AF:
0.00196
ESP6500AA
AF:
0.00507
AC:
16
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000685
AC:
20

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Apr 04, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.2
DANN
Benign
0.84
DEOGEN2
Benign
0.0067
T;T;.
FATHMM_MKL
Benign
0.017
N
LIST_S2
Benign
0.36
T;T;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.0048
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.69
N;.;.
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.82
N;N;N
REVEL
Benign
0.0090
Sift
Benign
0.17
T;T;T
Sift4G
Benign
0.071
T;T;T
Polyphen
0.61
P;.;.
Vest4
0.078
MutPred
0.16
Loss of ubiquitination at K166 (P = 0.0818);.;.;
MVP
0.63
MPC
0.019
ClinPred
0.0066
T
GERP RS
1.7
Varity_R
0.086
gMVP
0.00041

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: rs144502161; hg19: chrX-80370502; API