Variant 22-24723214-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001255975.1(PIWIL3):c.2273C>T(p.Thr758Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PIWIL3
NM_001255975.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

Variant links:

Genes affected

PIWIL3 (HGNC:18443): (piwi like RNA-mediated gene silencing 3) This gene encodes a member of the PIWI subfamily of Argonaute family proteins. This subfamily of proteins contains a PAZ domain, found in proteins involved in RNA-mediated gene silencing, and a C-terminal Piwi domain. The encoded protein is thought to function in maintenance of germline cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

PIWIL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PIWIL3	NM_001255975.1 linkuse as main transcript	c.2273C>T	p.Thr758Ile	missense_variant	19/21	ENST00000616349.5
PIWIL3	NM_001008496.3 linkuse as main transcript	c.2300C>T	p.Thr767Ile	missense_variant	19/21
PIWIL3	NR_045648.1 linkuse as main transcript	n.2904C>T		non_coding_transcript_exon_variant	20/22
PIWIL3	NR_045649.2 linkuse as main transcript	n.2777C>T		non_coding_transcript_exon_variant	20/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PIWIL3	ENST00000616349.5 linkuse as main transcript	c.2273C>T	p.Thr758Ile	missense_variant	19/21	1	NM_001255975.1	A2
PIWIL3	ENST00000332271.9 linkuse as main transcript	c.2300C>T	p.Thr767Ile	missense_variant	19/21	1		P2
PIWIL3	ENST00000527701.6 linkuse as main transcript	c.*2245C>T		3_prime_UTR_variant, NMD_transcript_variant	20/22	1
PIWIL3	ENST00000533313.6 linkuse as main transcript	c.*2199C>T		3_prime_UTR_variant, NMD_transcript_variant	20/22	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458016

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725602

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.2300C>T (p.T767I) alteration is located in exon 19 (coding exon 18) of the PIWIL3 gene. This alteration results from a C to T substitution at nucleotide position 2300, causing the threonine (T) at amino acid position 767 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T;.;.

Eigen

Uncertain

0.36

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.72

T;.;.;T

M_CAP

Benign

0.0042

MetaRNN

Uncertain

0.66

D;D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

3.2

M;M;.;.

MutationTaster

Benign

0.63

N;N;N

PrimateAI

Uncertain

0.55

Sift4G

Uncertain

0.023

D;D;D;D

Polyphen

0.99

D;D;D;D

Vest4

0.51

MutPred

0.73

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);.;.;

MVP

0.48

MPC

0.53

ClinPred

0.97

GERP RS

1.5

Varity_R

0.10

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over