Genetic Variant PABPN1L:p.Val205Met (chr16-88864894-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080487.4(PABPN1L):c.613G>A(p.Val205Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,594,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

PABPN1L
NM_001080487.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.681

Publications

0 publications found

Variant links:

Genes affected

PABPN1L (HGNC:37237): (PABPN1 like, cytoplasmic) Predicted to enable RNA binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PABPN1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019220978).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080487.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PABPN1L	NM_001080487.4	MANE Select	c.613G>A	p.Val205Met	missense	Exon 5 of 7	NP_001073956.2	A6NDY0-1
PABPN1L	NM_001385709.2		c.506G>A	p.Arg169His	missense	Exon 4 of 6	NP_001372638.1
PABPN1L	NM_001294328.4		c.566+128G>A		intron	N/A	NP_001281257.1	A6NDY0-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PABPN1L	ENST00000419291.7	TSL:1 MANE Select	c.613G>A	p.Val205Met	missense	Exon 5 of 7	ENSP00000408598.2	A6NDY0-1
PABPN1L	ENST00000547152.1	TSL:1	c.506G>A	p.Arg169His	missense	Exon 4 of 6	ENSP00000449247.1	A0A1C7CYY8
PABPN1L	ENST00000411789.6	TSL:1	c.566+128G>A		intron	N/A	ENSP00000405259.2	A6NDY0-2

Frequencies

GnomAD3 genomes

AF:

0.000121

AC:

AN:

149266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000735

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000620

Gnomad SAS

AF:

0.00152

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000745

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000151

AC:

AN:

244302

AF XY:

0.000195

show subpopulations

Gnomad AFR exome

AF:

0.000137

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000454

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000726

AC:

105

AN:

1445566

Hom.:

Cov.:

AF XY:

0.0000960

AC XY:

AN XY:

718856

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32864

American (AMR)

AF:

0.00

AC:

AN:

44136

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25472

East Asian (EAS)

AF:

0.000104

AC:

AN:

38644

South Asian (SAS)

AF:

0.000827

AC:

AN:

85896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0000227

AC:

AN:

1102314

Other (OTH)

AF:

0.0000169

AC:

AN:

59256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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:

0.000120

AC:

AN:

149398

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

AN XY:

73066

show subpopulations

African (AFR)

AF:

0.0000733

AC:

AN:

40952

American (AMR)

AF:

0.00

AC:

AN:

15094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3420

East Asian (EAS)

AF:

0.000620

AC:

AN:

4836

South Asian (SAS)

AF:

0.00152

AC:

AN:

4606

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000745

AC:

AN:

67098

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000256

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000174

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

-0.47

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.35

M_CAP

Benign

0.016

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

PhyloP100

0.68

PROVEAN

Benign

2.1

REVEL

Benign

0.048

Sift

Benign

0.13

MVP

0.11

ClinPred

0.029

GERP RS

-0.39

Varity_R

0.031

Mutation Taster

=90/10

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over