Genetic Variant NM_153339.3:c.232C>G (chr1-1309182-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153339.3(PUSL1):c.232C>G(p.Leu78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,389,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PUSL1
NM_153339.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.982

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=0.067017555).

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.232C>G	p.Leu78Val	missense	Exon 3 of 8	NP_699170.1	Q8N0Z8-1
PUSL1	NM_001346116.2		c.232C>G	p.Leu78Val	missense	Exon 3 of 8	NP_001333045.1
PUSL1	NR_144369.2		n.221C>G		non_coding_transcript_exon	Exon 2 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PUSL1	ENST00000379031.10	TSL:1 MANE Select	c.232C>G	p.Leu78Val	missense	Exon 3 of 8	ENSP00000368318.5	Q8N0Z8-1
PUSL1	ENST00000892133.1		c.232C>G	p.Leu78Val	missense	Exon 3 of 8	ENSP00000562192.1
PUSL1	ENST00000892132.1		c.211C>G	p.Leu71Val	missense	Exon 3 of 8	ENSP00000562191.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1389886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

687522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31392

American (AMR)

AF:

0.00

AC:

AN:

36492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24612

East Asian (EAS)

AF:

0.00

AC:

AN:

36330

South Asian (SAS)

AF:

0.00

AC:

AN:

79208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5248

European-Non Finnish (NFE)

AF:

0.00000184

AC:

AN:

1084674

Other (OTH)

AF:

0.00

AC:

AN:

57806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.017

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.73

M_CAP

Benign

0.029

MetaRNN

Benign

0.067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.030

PhyloP100

-0.98

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.19

REVEL

Benign

0.073

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.16

MutPred

0.68

Gain of MoRF binding (P = 0.1282)

MVP

0.085

MPC

0.081

ClinPred

0.068

GERP RS

-1.2

PromoterAI

-0.084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.049

gMVP

0.24

Mutation Taster

=99/1

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