NM_001080487.4:c.601G>C

Variant names:

• chr16-88864906-C-G
• rs780812870
• NM_001080487.4:c.601G>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.601G>C​(p.Val201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 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. 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. V201M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PABPN1L NM_001080487.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.21391088).

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>C	p.Val201Leu	missense	Exon 5 of 7	NP_001073956.2	A6NDY0-1
	PABPN1L	NM_001385709.2		c.494G>C	p.Arg165Pro	missense	Exon 4 of 6	NP_001372638.1
	PABPN1L	NM_001294328.4		c.566+116G>C		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>C	p.Val201Leu	missense	Exon 5 of 7	ENSP00000408598.2	A6NDY0-1
	PABPN1L	ENST00000547152.1	TSL:1	c.494G>C	p.Arg165Pro	missense	Exon 4 of 6	ENSP00000449247.1	A0A1C7CYY8
	PABPN1L	ENST00000411789.6	TSL:1	c.566+116G>C		intron	N/A	ENSP00000405259.2	A6NDY0-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454078 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 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: 0.00 AC: 0 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: 0.00000180 AC: 2 AN: 1108118

Other (OTH) AF: 0.00 AC: 0 AN: 60016

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.27	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.38	T
PhyloP100		2.0
PROVEAN	Benign	1.6	N
REVEL	Benign	0.14
Sift	Benign	0.34	T
MutPred		0.28		Loss of MoRF binding (P = 5e-04)
MVP		0.18
ClinPred		0.61	D
GERP RS		5.4
Varity_R		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;