rs1401656265

Variant names:

• chr14-23321490-GGCA-G
• rs1401656265
• NM_004643.4:c.30_32delAGC

Your query was ambiguous. Multiple possible variants found:

• chr14-23321490-GGCA-G
• chr14-23321490-GGCA-GGCAGCA
• chr14-23321490-GGCA-GGCAGCAGCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_004643.4(PABPN1):​c.30_32delAGC​(p.Ala11del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 1,198,106 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: PABPN1 NM_004643.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 0 publications found

Genes affected

PABPN1 (HGNC:8565): (poly(A) binding protein nuclear 1) This gene encodes an abundant nuclear protein that binds with high affinity to nascent poly(A) tails. The protein is required for progressive and efficient polymerization of poly(A) tails at the 3' ends of eukaryotic transcripts and controls the size of the poly(A) tail to about 250 nt. At steady-state, this protein is localized in the nucleus whereas a different poly(A) binding protein is localized in the cytoplasm. This gene contains a GCG trinucleotide repeat at the 5' end of the coding region, and expansion of this repeat from the normal 6 copies to 8-13 copies leads to autosomal dominant oculopharyngeal muscular dystrophy (OPMD) disease. Related pseudogenes have been identified on chromosomes 19 and X. Read-through transcription also exists between this gene and the neighboring upstream BCL2-like 2 (BCL2L2) gene. [provided by RefSeq, Dec 2010]

BCL2L2-PABPN1 (HGNC:42959): (BCL2L2-PABPN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring BCL2L2 (BCL2-like 2) and PABPN1 (poly(A) binding protein, nuclear 1) genes on chromosome 14. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PABPN1	NM_004643.4	c.30_32delAGC	p.Ala11del	disruptive_inframe_deletion	Exon 1 of 7	ENST00000216727.9	NP_004634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PABPN1	ENST00000216727.9	c.30_32delAGC	p.Ala11del	disruptive_inframe_deletion	Exon 1 of 7	1	NM_004643.4	ENSP00000216727.4
BCL2L2-PABPN1	ENST00000553781.5	c.433-682_433-680delAGC		intron_variant	Intron 3 of 8	2		ENSP00000451320.1

Frequencies

GnomAD3 genomes AF: 0.00000663 AC: 1 AN: 150828 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 7014 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ 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: 0.00000573 AC: 6 AN: 1047278 Hom.: 0 AF XY: 0.00000604 AC XY: 3 AN XY: 497090

African (AFR) AF: 0.00 AC: 0 AN: 21354

American (AMR) AF: 0.00 AC: 0 AN: 7034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12336

East Asian (EAS) AF: 0.00 AC: 0 AN: 22636

South Asian (SAS) AF: 0.00 AC: 0 AN: 19364

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2728

European-Non Finnish (NFE) AF: 0.00000668 AC: 6 AN: 898008

Other (OTH) AF: 0.00 AC: 0 AN: 40588

GnomAD4 genome AF: 0.00000663 AC: 1 AN: 150828 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73640

African (AFR) AF: 0.00 AC: 0 AN: 41274

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67608

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1401656265; hg19: chr14-23790699;