chr21-39345211-C-T

Variant names:

• chr21-39345211-C-T
• rs139139360
• NM_004965.7:c.190G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004965.7(HMGN1):​c.190G>A​(p.Glu64Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000338 in 1,613,594 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00034 (2 hom.)
• Consequence: HMGN1 NM_004965.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.45
• Publications: 5 publications found

Genes affected

HMGN1 (HGNC:4984): (high mobility group nucleosome binding domain 1) The protein encoded by this gene binds nucleosomal DNA and is associated with transcriptionally active chromatin. Along with a similar protein, HMG17, the encoded protein may help maintain an open chromatin configuration around transcribable genes. [provided by RefSeq, Aug 2011]

LOC124905074 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09216756).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004965.7. 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
	HMGN1	NM_004965.7	MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 5 of 6	NP_004956.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGN1	ENST00000380749.10	TSL:1 MANE Select	c.190G>A	p.Glu64Lys	missense	Exon 5 of 6	ENSP00000370125.5	P05114
	HMGN1	ENST00000380747.5	TSL:3	c.238G>A	p.Glu80Lys	missense	Exon 5 of 6	ENSP00000370123.1	A6NEL0
	HMGN1	ENST00000910672.1		c.190G>A	p.Glu64Lys	missense	Exon 6 of 7	ENSP00000580731.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152008 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000460

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000410 AC: 103 AN: 251146 AF XY: 0.000457

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000484

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000342 AC: 500 AN: 1461468 Hom.: 2 Cov.: 33 AF XY: 0.000363 AC XY: 264 AN XY: 727040

African (AFR) AF: 0.0000897 AC: 3 AN: 33462

American (AMR) AF: 0.000157 AC: 7 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000880 AC: 23 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39692

South Asian (SAS) AF: 0.000742 AC: 64 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00287 AC: 16 AN: 5572

European-Non Finnish (NFE) AF: 0.000320 AC: 356 AN: 1111954

Other (OTH) AF: 0.000447 AC: 27 AN: 60338

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152126 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74380

African (AFR) AF: 0.0000241 AC: 1 AN: 41502

American (AMR) AF: 0.000459 AC: 7 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000343 Hom.: 1

Bravo AF: 0.000261

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000288 AC: 35

EpiCase AF: 0.000654

EpiControl AF: 0.000831

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.055
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.4	L
PhyloP100		5.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.15
Sift	Benign	0.32	T
Sift4G	Benign	0.58	T
Polyphen		0.0070	B
Vest4		0.62
MVP		0.43
MPC		0.0067
ClinPred		0.045	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.047
Mutation Taster		=94/6	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

Other links and lift over

dbSNP: rs139139360; hg19: chr21-40717137;