16-88864906-C-T

Variant names:

• chr16-88864906-C-T
• rs780812870
• NM_001080487.4:c.601G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080487.4(PABPN1L):​c.601G>A​(p.Val201Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000619 in 1,454,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 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: 0.0000062 (0 hom.)
• Consequence: PABPN1L NM_001080487.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25799754).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPN1L	NM_001080487.4	MANE Select	c.601G>A	p.Val201Met	missense	Exon 5 of 7	NP_001073956.2	A6NDY0-1
	PABPN1L	NM_001385709.2		c.494G>A	p.Arg165His	missense	Exon 4 of 6	NP_001372638.1
	PABPN1L	NM_001294328.4		c.566+116G>A		intron	N/A	NP_001281257.1	A6NDY0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PABPN1L	ENST00000419291.7	TSL:1 MANE Select	c.601G>A	p.Val201Met	missense	Exon 5 of 7	ENSP00000408598.2	A6NDY0-1
	PABPN1L	ENST00000547152.1	TSL:1	c.494G>A	p.Arg165His	missense	Exon 4 of 6	ENSP00000449247.1	A0A1C7CYY8
	PABPN1L	ENST00000411789.6	TSL:1	c.566+116G>A		intron	N/A	ENSP00000405259.2	A6NDY0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244524 AF XY: 0.00000748

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000619 AC: 9 AN: 1454078 Hom.: 0 Cov.: 38 AF XY: 0.00000691 AC XY: 5 AN XY: 723244

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25878

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1108118

Other (OTH) AF: 0.0000167 AC: 1 AN: 60016

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000831 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
Eigen	Benign	0.10
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	-0.20	T
PhyloP100		2.0
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.13
Sift	Benign	0.32	T
MutPred		0.22		Loss of MoRF binding (P = 0.0092)
MVP		0.17
ClinPred		0.84	D
GERP RS		5.4
Varity_R		0.18
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs780812870; hg19: chr16-88931314;