Genetic Variant NM_006236.3:c.120_122dupCGG (chr2-104855612-T-TGGC) – 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.120_122dupCGG(p.Gly41dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 643,494 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 1 hom., cov: 25)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

POU3F3
NM_006236.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

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:

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ACMG classification

Classification was made for transcript

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

BP6

Variant 2-104855612-T-TGGC is Benign according to our data. Variant chr2-104855612-T-TGGC is described in ClinVar as Likely_benign. ClinVar VariationId is 2651215.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 79 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.120_122dupCGG	p.Gly41dup	disruptive_inframe_insertion	Exon 1 of 1	NP_006227.1	P20264
POU3F3	NM_001433704.1		c.120_122dupCGG	p.Gly41dup	disruptive_inframe_insertion	Exon 2 of 2	NP_001420633.1	P20264
POU3F3	NR_197431.1		n.294+2061_294+2063dupCGG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.120_122dupCGG	p.Gly41dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000355001.2	P20264
POU3F3	ENST00000674056.1		c.120_122dupCGG	p.Gly41dup	disruptive_inframe_insertion	Exon 4 of 4	ENSP00000501036.1	P20264
ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1798_345+1800dupCGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00333

AC:

AN:

23752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0190

Gnomad SAS

AF:

0.00430

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0556

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00110

AC:

682

AN:

619718

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

328

AN XY:

287932

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

11612

American (AMR)

AF:

0.00128

AC:

AN:

784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3894

East Asian (EAS)

AF:

0.00668

AC:

AN:

2846

South Asian (SAS)

AF:

0.000995

AC:

AN:

13070

European-Finnish (FIN)

AF:

0.00314

AC:

AN:

318

Middle Eastern (MID)

AF:

0.000833

AC:

AN:

1200

European-Non Finnish (NFE)

AF:

0.00109

AC:

615

AN:

565516

Other (OTH)

AF:

0.000635

AC:

AN:

20478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

114

143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

160

<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

AF:

0.00332

AC:

AN:

23776

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

AN XY:

11904

show subpopulations

African (AFR)

AF:

0.00261

AC:

AN:

6520

American (AMR)

AF:

0.00223

AC:

AN:

2246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

626

East Asian (EAS)

AF:

0.0191

AC:

AN:

996

South Asian (SAS)

AF:

0.00431

AC:

AN:

696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

760

Middle Eastern (MID)

AF:

0.0556

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00297

AC:

AN:

11432

Other (OTH)

AF:

0.00

AC:

AN:

352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000614

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

0.11

Mutation Taster

=87/13

polymorphism

(source)

Splicing

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

Publications

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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