16-88864301-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001080487.4(PABPN1L):​c.733G>T​(p.Gly245Trp) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G245R) has been classified as Uncertain significance.

• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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>T	p.Gly245Trp	missense	Exon 6 of 7	NP_001073956.2	A6NDY0-1
	PABPN1L	NM_001385709.2		c.626G>T	p.Gly209Val	missense	Exon 5 of 6	NP_001372638.1
	PABPN1L	NM_001294328.4		c.645G>T	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>T	p.Gly245Trp	missense	Exon 6 of 7	ENSP00000408598.2	A6NDY0-1
	PABPN1L	ENST00000547152.1	TSL:1	c.626G>T	p.Gly209Val	missense	Exon 5 of 6	ENSP00000449247.1	A0A1C7CYY8
	PABPN1L	ENST00000411789.6	TSL:1	c.645G>T	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: 0.00000144 AC XY: 1 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	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.091
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.27	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	0.56	D
PhyloP100		1.7
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.17
Sift	Benign	0.059	T
MutPred		0.13		Gain of sheet (P = 0.0061)
MVP		0.21
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.70		Position offset: 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;