Genetic Variant PABPN1L:p.Arg268His (chr16-88863790-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.803G>A(p.Arg268His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,536,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

PABPN1L
NM_001080487.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.380

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=0.008474797).

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.803G>A	p.Arg268His	missense	Exon 7 of 7	NP_001073956.2	A6NDY0-1
PABPN1L	NM_001294328.4		c.715G>A	p.Val239Met	missense	Exon 6 of 6	NP_001281257.1	A6NDY0-2
PABPN1L	NM_001385709.2		c.696G>A	p.Pro232Pro	synonymous	Exon 6 of 6	NP_001372638.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PABPN1L	ENST00000419291.7	TSL:1 MANE Select	c.803G>A	p.Arg268His	missense	Exon 7 of 7	ENSP00000408598.2	A6NDY0-1
PABPN1L	ENST00000411789.6	TSL:1	c.715G>A	p.Val239Met	missense	Exon 6 of 6	ENSP00000405259.2	A6NDY0-2
PABPN1L	ENST00000547152.1	TSL:1	c.696G>A	p.Pro232Pro	synonymous	Exon 6 of 6	ENSP00000449247.1	A0A1C7CYY8

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000190

AC:

AN:

136976

AF XY:

0.000148

show subpopulations

Gnomad AFR exome

AF:

0.000774

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00143

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.000477

GnomAD4 exome

AF:

0.0000658

AC:

AN:

1383658

Hom.:

Cov.:

AF XY:

0.0000557

AC XY:

AN XY:

682762

show subpopulations

African (AFR)

AF:

0.000665

AC:

AN:

31594

American (AMR)

AF:

0.000140

AC:

AN:

35690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25172

East Asian (EAS)

AF:

0.000840

AC:

AN:

35734

South Asian (SAS)

AF:

0.0000884

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.0000295

AC:

AN:

33848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00000742

AC:

AN:

1078806

Other (OTH)

AF:

0.000328

AC:

AN:

57910

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.000315

AC:

AN:

152374

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74514

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000514

Hom.:

Bravo

AF:

0.000366

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000142

AC:

Asia WGS

AF:

0.00462

AC:

AN:

3478

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

-0.55

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.46

M_CAP

Benign

0.023

MetaRNN

Benign

0.0085

MetaSVM

Benign

-0.96

PhyloP100

0.38

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.019

Sift

Benign

0.076

Sift4G

Benign

0.13

Polyphen

0.035

Vest4

0.17

MutPred

0.33

Loss of methylation at R268 (P = 0.0071)

MVP

0.055

MPC

0.010

ClinPred

0.016

GERP RS

-0.32

Varity_R

0.062

gMVP

0.60

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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