rs540307276

Variant names:

• chr8-143824349-TGCCGCCGCC-T
• rs540307276
• NM_078480.3:c.66_74delGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr8-143824349-TGCCGCCGCC-T
• chr8-143824349-TGCCGCCGCC-TGCC
• chr8-143824349-TGCCGCCGCC-TGCCGCC
• chr8-143824349-TGCCGCCGCC-TGCCGCCGCCGCC
• chr8-143824349-TGCCGCCGCC-TGCCGCCGCCGCCGCC

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP3 BS2

The NM_078480.3(PUF60):​c.66_74delGGCGGCGGC​(p.Ala23_Ala25del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,050 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A22A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PUF60 NM_078480.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

PUF60 (HGNC:17042): (poly(U) binding splicing factor 60) This gene encodes a nucleic acid-binding protein that plays a role in a variety of nuclear processes, including pre-mRNA splicing and transcriptional regulation. The encoded protein forms a complex with the far upstream DNA element (FUSE) and FUSE-binding protein at the myelocytomatosis oncogene (MYC) promoter. This complex represses MYC transcription through the core-TFIIH basal transcription factor. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

PUF60 Gene-Disease associations (from GenCC):

• 8q24.3 microdeletion syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_078480.3
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_078480.3. 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
	PUF60	NM_078480.3	MANE Select	c.66_74delGGCGGCGGC	p.Ala23_Ala25del	disruptive_inframe_deletion	Exon 2 of 12	NP_510965.1	Q9UHX1-1
	PUF60	NM_001362895.2		c.177_185delGGCGGCGGC	p.Ala60_Ala62del	disruptive_inframe_deletion	Exon 3 of 13	NP_001349824.1	E9PL19
	PUF60	NM_001362896.2		c.177_185delGGCGGCGGC	p.Ala60_Ala62del	disruptive_inframe_deletion	Exon 3 of 13	NP_001349825.1	E9PL19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PUF60	ENST00000526683.6	TSL:1 MANE Select	c.66_74delGGCGGCGGC	p.Ala23_Ala25del	disruptive_inframe_deletion	Exon 2 of 12	ENSP00000434359.1	Q9UHX1-1
	PUF60	ENST00000349157.10	TSL:1	c.66_74delGGCGGCGGC	p.Ala23_Ala25del	disruptive_inframe_deletion	Exon 2 of 11	ENSP00000322036.7	Q9UHX1-2
	PUF60	ENST00000453551.6	TSL:1	c.-64_-56delGGCGGCGGC		5_prime_UTR	Exon 2 of 12	ENSP00000402953.2	Q9UHX1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240516 AF XY: 0.00000759

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: 0.00000932

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460050 Hom.: 0 AF XY: 0.00000138 AC XY: 1 AN XY: 726360

African (AFR) AF: 0.0000598 AC: 2 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111638

Other (OTH) AF: 0.00 AC: 0 AN: 60258

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs540307276; hg19: chr8-144906519;