NM_153216.2:c.478A>C

Variant names:

• chr5-93741086-T-G
• NM_153216.2:c.478A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153216.2(POU5F2):​c.478A>C​(p.Ser160Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POU5F2 NM_153216.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.442
• Publications: 0 publications found

Genes affected

POU5F2 (HGNC:26367): (POU domain class 5, transcription factor 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ARB2A (HGNC:25365): (ARB2 cotranscriptional regulator A) Predicted to contribute to siRNA binding activity. Predicted to be involved in heterochromatin assembly by small RNA; neural crest cell development; and regulation of alternative mRNA splicing, via spliceosome. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153216.2. 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
	POU5F2	NM_153216.2	MANE Select	c.478A>C	p.Ser160Arg	missense	Exon 1 of 1	NP_694948.1	Q8N7G0
	ARB2A	NM_032042.6	MANE Select	c.1108+35073A>C		intron	N/A	NP_114431.2
	ARB2A	NM_001163417.1		c.970+35073A>C		intron	N/A	NP_001156889.1	Q8WUF8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F2	ENST00000606183.4	TSL:6 MANE Select	c.478A>C	p.Ser160Arg	missense	Exon 1 of 1	ENSP00000489796.1	Q8N7G0
	ARB2A	ENST00000395965.8	TSL:1 MANE Select	c.1108+35073A>C		intron	N/A	ENSP00000379294.3	Q8WUF8-1
	ARB2A	ENST00000881906.1		c.1144+2451A>C		intron	N/A	ENSP00000551965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	23
DANN	Benign	0.55
DEOGEN2	Pathogenic	0.85	D
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.88	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.44
PrimateAI	Uncertain	0.58	T
Polyphen		1.0	D
GERP RS		2.8
Varity_R		0.14
gMVP		0.94
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr5-93076792;