15-59514274-A-AT

Position:

• chr15-59514274-A-AT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PVS1_Strong BA1

The NM_152450.3(FAM81A):​c.651-3dupT variant causes a splice acceptor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 791,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FAM81A NM_152450.3 splice_acceptor, intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.10

Genes affected

FAM81A (HGNC:28379): (family with sequence similarity 81 member A)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.12195122 fraction of the gene. Cryptic splice site detected, with MaxEntScore 10, offset of 0 (no position change), new splice context is: tgcaatttttttttttttAGatt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM81A	NM_152450.3	c.651-3dupT		splice_acceptor_variant, intron_variant		ENST00000288228.10	NP_689663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM81A	ENST00000288228.10	c.651-3dupT		splice_acceptor_variant, intron_variant		1	NM_152450.3	ENSP00000288228.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 96 AN: 147594 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000692

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000678

Gnomad ASJ AF: 0.000882

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.00107

Gnomad FIN AF: 0.00158

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000406

Gnomad OTH AF: 0.00197

GnomAD4 exome AF: 0.0713 AC: 56461 AN: 791332 Hom.: 0 Cov.: 23 AF XY: 0.0726 AC XY: 28717 AN XY: 395364

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.0926

Gnomad4 ASJ exome AF: 0.0888

Gnomad4 EAS exome AF: 0.0823

Gnomad4 SAS exome AF: 0.0995

Gnomad4 FIN exome AF: 0.0578

Gnomad4 NFE exome AF: 0.0682

Gnomad4 OTH exome AF: 0.0771

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000650 AC: 96 AN: 147660 Hom.: 0 Cov.: 32 AF XY: 0.000668 AC XY: 48 AN XY: 71858

Gnomad4 AFR AF: 0.000691

Gnomad4 AMR AF: 0.000677

Gnomad4 ASJ AF: 0.000882

Gnomad4 EAS AF: 0.000589

Gnomad4 SAS AF: 0.00107

Gnomad4 FIN AF: 0.00158

Gnomad4 NFE AF: 0.000406

Gnomad4 OTH AF: 0.00195

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

CIC-rearranged sarcoma Other:1

not provided, no classification provided

literature only

Children's Cancer Therapy Development Institute

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Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs747487795; hg19: chr15-59806473;