rs3130931

Variant names:

• chr6-31167111-T-A
• rs3130931
• ENST00000513407.1:c.-1472A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31167111-T-A
• chr6-31167111-T-C
• chr6-31167111-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203289.6(POU5F1):​c.-1169A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU5F1 NM_203289.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.491
• Publications: 60 publications found

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203289.6. 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
	POU5F1	NM_002701.6	MANE Select	c.406-1064A>T		intron	N/A	NP_002692.2
	POU5F1	NM_001173531.3		c.-683A>T		5_prime_UTR	Exon 1 of 5	NP_001167002.1	M1S623
	POU5F1	NM_203289.6		c.-1169A>T		5_prime_UTR	Exon 1 of 4	NP_976034.4	M1S623

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000513407.1	TSL:1	c.-1472A>T		5_prime_UTR	Exon 1 of 3	ENSP00000475512.1	F2Z381
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.406-1064A>T		intron	N/A	ENSP00000259915.7	Q01860-1
	POU5F1	ENST00000441888.7	TSL:1	c.-183-1064A>T		intron	N/A	ENSP00000389359.2	F2Z381

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000318 AC: 1 AN: 314690 Hom.: 0 Cov.: 3 AF XY: 0.00000580 AC XY: 1 AN XY: 172268

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9254

American (AMR) AF: 0.00 AC: 0 AN: 17300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13228

East Asian (EAS) AF: 0.00 AC: 0 AN: 17540

South Asian (SAS) AF: 0.00 AC: 0 AN: 48318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2964

European-Non Finnish (NFE) AF: 0.00000564 AC: 1 AN: 177462

Other (OTH) AF: 0.00 AC: 0 AN: 17928

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 160044

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.9
DANN	Benign	0.62
PhyloP100		0.49
PromoterAI		-0.015	Neutral

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: rs3130931; hg19: chr6-31134888;