Variant 13-78601996-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_006237.4(POU4F1):c.679G>A(p.Gly227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000612 in 931,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

POU4F1
NM_006237.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.17

Variant links:

Genes affected

POU4F1 (HGNC:9218): (POU class 4 homeobox 1) This gene encodes a member of the POU-IV class of neural transcription factors. This protein is expressed in a subset of retinal ganglion cells and may be involved in the developing sensory nervous system. This protein may also promote the growth of cervical tumors. A translocation of this gene is associated with some adult acute myeloid leukemias. [provided by RefSeq, Mar 2012]

POU4F1 links:

POU4F1 (HGNC:):

POU4F1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.331303).

BS2

High AC in GnomAdExome4 at 55 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU4F1	NM_006237.4 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	2/2	ENST00000377208.7	NP_006228.3	Q01851-1
POU4F1	XR_007063683.1 linkuse as main transcript	n.1159G>A		non_coding_transcript_exon_variant	1/2
OBI1-AS1	NR_047001.1 linkuse as main transcript	n.385-3305C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU4F1	ENST00000377208.7 linkuse as main transcript	c.679G>A	p.Gly227Ser	missense_variant	2/2	1	NM_006237.4	ENSP00000366413.4		Q01851-1

Frequencies

GnomAD3 genomes

AF:

0.0000139

AC:

AN:

144272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000690

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:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000699

AC:

AN:

787004

Hom.:

Cov.:

AF XY:

0.0000712

AC XY:

AN XY:

365054

show subpopulations

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:

0.0000752

Gnomad4 OTH exome

AF:

0.0000387

GnomAD4 genome

AF:

0.0000139

AC:

AN:

144272

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

70174

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000690

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000153

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Ataxia, intention tremor, and hypotonia syndrome, childhood-onset

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Goettingen

Oct 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

0.0075

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.061

Eigen

Benign

-0.030

Eigen_PC

Benign

0.014

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.51

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.53

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.84

REVEL

Uncertain

0.34

Sift

Benign

0.32

Sift4G

Benign

0.39

Polyphen

0.98

Vest4

0.18

MutPred

0.47

Gain of glycosylation at G227 (P = 0);

MVP

0.61

ClinPred

0.40

GERP RS

3.1

Varity_R

0.14

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over