13-78601637-C-G

Variant names:

• chr13-78601637-C-G
• rs371001596
• NM_006237.4:c.1038G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006237.4(POU4F1):​c.1038G>C​(p.Lys346Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K346K) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POU4F1 NM_006237.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 1 publications found

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]

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1171186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006237.4. 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
	POU4F1	NM_006237.4	MANE Select	c.1038G>C	p.Lys346Asn	missense	Exon 2 of 2	NP_006228.3
	OBI1-AS1	NR_047001.1		n.385-3664C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU4F1	ENST00000377208.7	TSL:1 MANE Select	c.1038G>C	p.Lys346Asn	missense	Exon 2 of 2	ENSP00000366413.4	Q01851-1
	OBI1-AS1	ENST00000430549.6	TSL:4	n.430-3664C>G		intron	N/A
	OBI1-AS1	ENST00000444769.7	TSL:4	n.404-3664C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250472 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461554 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727100

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152182 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	-0.15	N
PhyloP100		0.89
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.28
Sift	Benign	0.21	T
Sift4G	Benign	0.50	T
Polyphen		0.38	B
Vest4		0.45
MutPred		0.37		Loss of ubiquitination at K346 (P = 8e-04)
MVP		0.26
ClinPred		0.39	T
GERP RS		3.3
Varity_R		0.22
gMVP		0.91
Mutation Taster		=41/59	disease causing

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

Other links and lift over

dbSNP: rs371001596; hg19: chr13-79175772;