Genetic Variant NM_001083116.3:c.*206_*209dupTTTT (chr10-70597843-T-TAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001083116.3(PRF1):c.*206_*209dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

PRF1
NM_001083116.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Publications

0 publications found

Variant links:

Genes affected

PRF1 (HGNC:9360): (perforin 1) This gene encodes a protein with structural similarities to complement component C9 that is important in immunity. This protein forms membrane pores that allow the release of granzymes and subsequent cytolysis of target cells. Whether pore formation occurs in the plasma membrane of target cells or in an endosomal membrane inside target cells is subject to debate. Mutations in this gene are associated with a variety of human disease including diabetes, multiple sclerosis, lymphomas, autoimmune lymphoproliferative syndrome (ALPS), aplastic anemia, and familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of early childhood. [provided by RefSeq, Aug 2017]

PRF1 links:

PALD1 (HGNC:23530): (phosphatase domain containing paladin 1) Predicted to enable protein tyrosine phosphatase activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

PALD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083116.3. 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
	PRF1	NM_001083116.3	MANE Select	c.206_209dupTTTT		3_prime_UTR	Exon 3 of 3	NP_001076585.1	P14222
	PRF1	NM_005041.6		c.206_209dupTTTT		3_prime_UTR	Exon 3 of 3	NP_005032.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRF1	ENST00000441259.2	TSL:5 MANE Select	c.206_209dupTTTT	3_prime_UTR	Exon 3 of 3	ENSP00000398568.1	P14222
PRF1	ENST00000373209.2	TSL:1	c.206_209dupTTTT	3_prime_UTR	Exon 3 of 3	ENSP00000362305.1	P14222
PRF1	ENST00000862973.1		c.206_209dupTTTT	3_prime_UTR	Exon 2 of 2	ENSP00000533032.1

Frequencies

GnomAD3 genomes

AF:

0.00000719

AC:

AN:

139116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000263

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000656

AC:

AN:

457570

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

240098

show subpopulations

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

African (AFR)

AF:

0.0000805

AC:

AN:

12418

American (AMR)

AF:

0.0000538

AC:

AN:

18600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13748

East Asian (EAS)

AF:

0.00

AC:

AN:

31204

South Asian (SAS)

AF:

0.00

AC:

AN:

43662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29066

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1984

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

280734

Other (OTH)

AF:

0.00

AC:

AN:

26154

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

AF:

0.00000719

AC:

AN:

139164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

67120

show subpopulations

African (AFR)

AF:

0.0000262

AC:

AN:

38140

American (AMR)

AF:

0.00

AC:

AN:

13662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3270

East Asian (EAS)

AF:

0.00

AC:

AN:

4650

South Asian (SAS)

AF:

0.00

AC:

AN:

4332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63844

Other (OTH)

AF:

0.00

AC:

AN:

1922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

140

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.6

Splicing

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

Publications

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NM_001083116.3:c.206_209dupTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over