Genetic Variant POU3F3:p.Ala44_Gly49del (chr2-104855627-CGGCGGGGGCGGCGCAGGG-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_006236.3(POU3F3):c.131_148delCAGGGGGCGGGGGCGGCG(p.Ala44_Gly49del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 570,308 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., cov: 6)

Exomes 𝑓: 0.000042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POU3F3
NM_006236.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

Genes affected

POU3F3 (HGNC:9216): (POU class 3 homeobox 3) This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system. [provided by RefSeq, Apr 2015]

POU3F3 links:

ENSG00000269707 (HGNC:):

ENSG00000269707 links:

PANTR1 (HGNC:49513): (POU3F3 adjacent non-coding transcript 1) Predicted to act upstream of or within regulation of gene expression. [provided by Alliance of Genome Resources, Apr 2022]

PANTR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 2-104855627-CGGCGGGGGCGGCGCAGGG-C is Benign according to our data. Variant chr2-104855627-CGGCGGGGGCGGCGCAGGG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2651216.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006236.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	NM_006236.3	MANE Select	c.131_148delCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	NP_006227.1	P20264
POU3F3	NM_001433704.1		c.131_148delCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49del	disruptive_inframe_deletion	Exon 2 of 2	NP_001420633.1	P20264
POU3F3	NR_197431.1		n.294+2072_294+2089delCAGGGGGCGGGGGCGGCG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.131_148delCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49del	disruptive_inframe_deletion	Exon 1 of 1	ENSP00000355001.2	P20264
POU3F3	ENST00000674056.1		c.131_148delCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49del	disruptive_inframe_deletion	Exon 4 of 4	ENSP00000501036.1	P20264
ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1809_345+1826delCAGGGGGCGGGGGCGGCG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000814

AC:

AN:

73708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000151

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:

0.000396

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000273

Gnomad OTH

AF:

0.00105

GnomAD4 exome

AF:

0.0000421

AC:

AN:

570308

Hom.:

AF XY:

0.0000378

AC XY:

AN XY:

264740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

10976

American (AMR)

AF:

0.00

AC:

AN:

746

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3520

East Asian (EAS)

AF:

0.000375

AC:

AN:

2666

South Asian (SAS)

AF:

0.000169

AC:

AN:

11858

European-Finnish (FIN)

AF:

0.00

AC:

AN:

244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1104

European-Non Finnish (NFE)

AF:

0.0000404

AC:

AN:

520410

Other (OTH)

AF:

0.00

AC:

AN:

18784

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000814

AC:

AN:

73708

Hom.:

Cov.:

AF XY:

0.0000848

AC XY:

AN XY:

35392

show subpopulations

African (AFR)

AF:

0.000151

AC:

AN:

19826

American (AMR)

AF:

0.00

AC:

AN:

6736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2002

East Asian (EAS)

AF:

0.00

AC:

AN:

2310

South Asian (SAS)

AF:

0.00

AC:

AN:

2080

European-Finnish (FIN)

AF:

0.000396

AC:

AN:

2528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

130

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

36678

Other (OTH)

AF:

0.00105

AC:

AN:

956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=169/31

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over