16-88864301-C-G

Variant names:

• chr16-88864301-C-G
• rs1183091214
• NM_001080487.4:c.733G>C

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.733G>C​(p.Gly245Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,403,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PABPN1L NM_001080487.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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=0.2069071).

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.733G>C	p.Gly245Arg	missense	Exon 6 of 7	NP_001073956.2	A6NDY0-1
	PABPN1L	NM_001385709.2		c.626G>C	p.Gly209Ala	missense	Exon 5 of 6	NP_001372638.1
	PABPN1L	NM_001294328.4		c.645G>C	p.Gly215Gly	synonymous	Exon 5 of 6	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.733G>C	p.Gly245Arg	missense	Exon 6 of 7	ENSP00000408598.2	A6NDY0-1
	PABPN1L	ENST00000547152.1	TSL:1	c.626G>C	p.Gly209Ala	missense	Exon 5 of 6	ENSP00000449247.1	A0A1C7CYY8
	PABPN1L	ENST00000411789.6	TSL:1	c.645G>C	p.Gly215Gly	synonymous	Exon 5 of 6	ENSP00000405259.2	A6NDY0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1403778 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 692994

African (AFR) AF: 0.00 AC: 0 AN: 31848

American (AMR) AF: 0.00 AC: 0 AN: 36868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.00 AC: 0 AN: 36120

South Asian (SAS) AF: 0.00 AC: 0 AN: 79488

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1081662

Other (OTH) AF: 0.00 AC: 0 AN: 58164

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.017
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.28	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.20	T
PhyloP100		1.7
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.16
Sift	Benign	0.30	T
MutPred		0.045		Loss of catalytic residue at P205 (P = 0.0914)
MVP		0.16
ClinPred		0.61	D
GERP RS		4.5
Varity_R		0.19
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1183091214; hg19: chr16-88930709;