chr21-39343143-T-C

Position:

• chr21-39343143-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004965.7(HMGN1):​c.272A>G​(p.Glu91Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: HMGN1 NM_004965.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.445

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115398616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGN1	NM_004965.7	c.272A>G	p.Glu91Gly	missense_variant	6/6	ENST00000380749.10
HMGN1	XM_024452071.2	c.163A>G	p.Lys55Glu	missense_variant	4/4
HMGN1	XM_047440757.1	c.163A>G	p.Lys55Glu	missense_variant	6/6
HMGN1	XM_047440758.1	c.163A>G	p.Lys55Glu	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGN1	ENST00000380749.10	c.272A>G	p.Glu91Gly	missense_variant	6/6	1	NM_004965.7	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.272A>G (p.E91G) alteration is located in exon 6 (coding exon 6) of the HMGN1 gene. This alteration results from a A to G substitution at nucleotide position 272, causing the glutamic acid (E) at amino acid position 91 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T;T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.77	T;T;T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.
MutationTaster	Benign	0.92	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-4.4	D;D;D
REVEL	Benign	0.052
Sift	Benign	0.060	T;T;D
Sift4G	Benign	0.50	T;T;T
Polyphen		0.0020	B;.;.
Vest4		0.088
MutPred		0.34		Gain of catalytic residue at P87 (P = 0.0776);.;.;
MVP		0.44
MPC		0.024
ClinPred		0.82	D
GERP RS		3.3
Varity_R		0.24
gMVP		0.036

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-40715069;