1-150226728-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001280560.2(ANP32E):​c.395G>A​(p.Arg132Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R132M) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: ANP32E NM_001280560.2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029976666).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001280560.2. 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>A	p.Glu187Glu	synonymous	Exon 5 of 7	NP_112182.1	Q9BTT0-1
	ANP32E	NM_001280560.2		c.395G>A	p.Arg132Lys	missense	Exon 4 of 5	NP_001267489.1	E9PLC4
	ANP32E	NM_001280559.2		c.561G>A	p.Glu187Glu	synonymous	Exon 5 of 7	NP_001267488.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANP32E	ENST00000583931.6	TSL:1 MANE Select	c.561G>A	p.Glu187Glu	synonymous	Exon 5 of 7	ENSP00000463154.1	Q9BTT0-1
	ANP32E	ENST00000533654.5	TSL:2	c.395G>A	p.Arg132Lys	missense	Exon 4 of 5	ENSP00000435215.1	E9PLC4
	ANP32E	ENST00000854339.1		c.561G>A	p.Glu187Glu	synonymous	Exon 5 of 7	ENSP00000524398.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152092 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 26

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152210 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74416

African (AFR) AF: 0.0000241 AC: 1 AN: 41528

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.3
DANN	Benign	0.60
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.13
PROVEAN	Benign	0.34	N
REVEL	Benign	0.068
Sift	Benign	1.0	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.21
MVP		0.41
ClinPred		0.046	T
GERP RS		-2.5
PromoterAI		-0.0045	Neutral
Mutation Taster		=98/2	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;