Genetic Variant PUSL1:p.Pro5Gln (chr1-1308657-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_153339.3(PUSL1):c.14C>A(p.Pro5Gln) variant causes a missense 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PUSL1
NM_153339.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42

Publications

0 publications found

Variant links:

Genes affected

PUSL1 (HGNC:26914): (pseudouridine synthase like 1) Predicted to enable pseudouridine synthase activity. Predicted to be involved in tRNA pseudouridine synthesis. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

PUSL1 links:

ACAP3 (HGNC:16754): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 3) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to act upstream of or within neuron migration and regulation of neuron projection development. Predicted to be located in growth cone. [provided by Alliance of Genome Resources, Apr 2022]

ACAP3 links:

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ACMG classification

Classification was made for transcript

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 (MetaRNN=0.114055276).

BP6

Variant 1-1308657-C-A is Benign according to our data. Variant chr1-1308657-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3149870.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153339.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUSL1	NM_153339.3	MANE Select	c.14C>A	p.Pro5Gln	missense	Exon 1 of 8	NP_699170.1	Q8N0Z8-1
PUSL1	NM_001346116.2		c.14C>A	p.Pro5Gln	missense	Exon 1 of 8	NP_001333045.1
PUSL1	NR_144369.2		n.61C>A		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUSL1	ENST00000379031.10	TSL:1 MANE Select	c.14C>A	p.Pro5Gln	missense	Exon 1 of 8	ENSP00000368318.5	Q8N0Z8-1
PUSL1	ENST00000892133.1		c.14C>A	p.Pro5Gln	missense	Exon 1 of 8	ENSP00000562192.1
PUSL1	ENST00000892132.1		c.14C>A	p.Pro5Gln	missense	Exon 1 of 8	ENSP00000562191.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1381918

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

684666

African (AFR)

AF:

0.00

AC:

AN:

28564

American (AMR)

AF:

0.00

AC:

AN:

33880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24128

East Asian (EAS)

AF:

0.00

AC:

AN:

31084

South Asian (SAS)

AF:

0.00

AC:

AN:

77892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48820

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4426

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076352

Other (OTH)

AF:

0.00

AC:

AN:

56772

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

1.6

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.024

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.27

M_CAP

Pathogenic

0.34

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

-1.4

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.82

REVEL

Benign

0.038

Sift

Benign

0.18

Sift4G

Benign

0.19

Polyphen

0.23

Vest4

0.18

MutPred

0.31

Gain of MoRF binding (P = 0.0163)

MVP

0.088

MPC

0.073

ClinPred

0.078

GERP RS

-0.23

PromoterAI

0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.031

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over