9-98011361-A-T

Position:

• chr9-98011361-A-T

Variant summary

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

The ENST00000339399.5(ANP32B):​c.608A>T​(p.Asp203Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ANP32B ENST00000339399.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

ANP32B (HGNC:16677): (acidic nuclear phosphoprotein 32 family member B) Enables RNA polymerase binding activity and histone binding activity. Involved in several processes, including activation of cysteine-type endopeptidase activity involved in apoptotic process; nucleosome assembly; and positive regulation of protein export from nucleus. Located in cytoplasm and nucleoplasm. Colocalizes with nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.18619153).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANP32B	NM_006401.3	c.608A>T	p.Asp203Val	missense_variant	5/7	ENST00000339399.5	NP_006392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANP32B	ENST00000339399.5	c.608A>T	p.Asp203Val	missense_variant	5/7	1	NM_006401.3	ENSP00000345848	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416804 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 700728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jun 10, 2022

The c.608A>T (p.D203V) alteration is located in exon 5 (coding exon 5) of the ANP32B gene. This alteration results from a A to T substitution at nucleotide position 608, causing the aspartic acid (D) at amino acid position 203 to be replaced by a valine (V). 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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.86
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.18
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.017	D
Polyphen		0.023	B
Vest4		0.35
MutPred		0.27		Loss of helix (P = 0.1706);
MVP		0.36
MPC		0.81
ClinPred		0.74	D
GERP RS		4.1
Varity_R		0.27
gMVP		0.013

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: chr9-100773643;