1-150226728-C-G

Variant names:

• chr1-150226728-C-G
• rs148947714
• NM_030920.5:c.561G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030920.5(ANP32E):​c.561G>C​(p.Glu187Asp) 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. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E187K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANP32E NM_030920.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• Publications: 0 publications found

Genes affected

ANP32E (HGNC:16673): (acidic nuclear phosphoprotein 32 family member E) Enables histone binding activity. Involved in histone exchange. Located in nucleus. Part of Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1501073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030920.5. 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
	ANP32E	NM_030920.5	MANE Select	c.561G>C	p.Glu187Asp	missense	Exon 5 of 7	NP_112182.1	Q9BTT0-1
	ANP32E	NM_001280559.2		c.561G>C	p.Glu187Asp	missense	Exon 5 of 7	NP_001267488.1
	ANP32E	NM_001136478.4		c.438G>C	p.Glu146Asp	missense	Exon 4 of 6	NP_001129950.1	Q9BTT0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANP32E	ENST00000583931.6	TSL:1 MANE Select	c.561G>C	p.Glu187Asp	missense	Exon 5 of 7	ENSP00000463154.1	Q9BTT0-1
	ANP32E	ENST00000854339.1		c.561G>C	p.Glu187Asp	missense	Exon 5 of 7	ENSP00000524398.1
	ANP32E	ENST00000933652.1		c.561G>C	p.Glu187Asp	missense	Exon 6 of 8	ENSP00000603711.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.74
DEOGEN2	Benign	0.060	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.13
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.16
Sift	Benign	0.58	T
Sift4G	Benign	0.56	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.20		Loss of phosphorylation at Y184 (P = 0.1509)
MVP		0.45
ClinPred		0.039	T
GERP RS		-2.5
PromoterAI		0.045	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.024
gMVP		0.0058
Mutation Taster		=84/16	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: rs148947714; hg19: chr1-150199060;