rs142173136

Variant names:

• chrX-81119810-C-A
• rs142173136
• NM_030763.3:c.23G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-81119810-C-A
• chrX-81119810-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_030763.3(HMGN5):​c.23G>T​(p.Gly8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,204,023 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,076 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., 51 hem., cov: 23)
  • Exomes 𝑓: 0.0030 (7 hom. 1025 hem.)
• Consequence: HMGN5 NM_030763.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0480
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006121278).
• BP6: Variant X-81119810-C-A is Benign according to our data. Variant chrX-81119810-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 782073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 51 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGN5	NM_030763.3	MANE Select	c.23G>T	p.Gly8Val	missense	Exon 3 of 7	NP_110390.1	P82970

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGN5	ENST00000358130.7	TSL:2 MANE Select	c.23G>T	p.Gly8Val	missense	Exon 3 of 7	ENSP00000350848.2	P82970
	HMGN5	ENST00000430960.5	TSL:1	c.23G>T	p.Gly8Val	missense	Exon 2 of 6	ENSP00000399626.1	Q5JSL0
	HMGN5	ENST00000916831.1		c.23G>T	p.Gly8Val	missense	Exon 2 of 7	ENSP00000586890.1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 229 AN: 111790 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000683

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000475

Gnomad ASJ AF: 0.00303

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000745

Gnomad FIN AF: 0.000497

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00354

Gnomad OTH AF: 0.00133

GnomAD2 exomes AF: 0.00167 AC: 305 AN: 182649 AF XY: 0.00171

Gnomad AFR exome AF: 0.000229

Gnomad AMR exome AF: 0.000476

Gnomad ASJ exome AF: 0.00201

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000438

Gnomad NFE exome AF: 0.00305

Gnomad OTH exome AF: 0.00266

GnomAD4 exome AF: 0.00303 AC: 3306 AN: 1092178 Hom.: 7 Cov.: 26 AF XY: 0.00286 AC XY: 1025 AN XY: 357840

African (AFR) AF: 0.000342 AC: 9 AN: 26298

American (AMR) AF: 0.000426 AC: 15 AN: 35175

Ashkenazi Jewish (ASJ) AF: 0.00217 AC: 42 AN: 19327

East Asian (EAS) AF: 0.00 AC: 0 AN: 30138

South Asian (SAS) AF: 0.000315 AC: 17 AN: 53941

European-Finnish (FIN) AF: 0.000494 AC: 20 AN: 40507

Middle Eastern (MID) AF: 0.000486 AC: 2 AN: 4117

European-Non Finnish (NFE) AF: 0.00364 AC: 3043 AN: 836771

Other (OTH) AF: 0.00344 AC: 158 AN: 45904

GnomAD4 genome AF: 0.00205 AC: 229 AN: 111845 Hom.: 0 Cov.: 23 AF XY: 0.00150 AC XY: 51 AN XY: 34019

African (AFR) AF: 0.000681 AC: 21 AN: 30829

American (AMR) AF: 0.000475 AC: 5 AN: 10529

Ashkenazi Jewish (ASJ) AF: 0.00303 AC: 8 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3563

South Asian (SAS) AF: 0.000747 AC: 2 AN: 2677

European-Finnish (FIN) AF: 0.000497 AC: 3 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00354 AC: 188 AN: 53134

Other (OTH) AF: 0.00131 AC: 2 AN: 1528

Alfa AF: 0.00298 Hom.: 122

Bravo AF: 0.00184

TwinsUK AF: 0.00458 AC: 17

ALSPAC AF: 0.00415 AC: 12

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.00476 AC: 32

ExAC AF: 0.00190 AC: 231

EpiCase AF: 0.00335

EpiControl AF: 0.00406

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Uncertain	0.97
DEOGEN2	Benign	0.0091	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.0061	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.048
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.051
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.021	D
Polyphen		0.11	B
Vest4		0.064
MVP		0.19
MPC		0.073
ClinPred		0.034	T
GERP RS		-2.1
Varity_R		0.17
gMVP		0.013
Mutation Taster		=86/14	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142173136; hg19: chrX-80375309;