2-152670383-TATAGCA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001365597.4(PRPF40A):c.1606-8_1606-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,600,622 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00070 (7 hom.)
• Consequence: PRPF40A NM_001365597.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.18

Genes affected

PRPF40A (HGNC:16463): (pre-mRNA processing factor 40 homolog A) Enables RNA binding activity. Involved in several processes, including cytoskeleton organization; regulation of cell shape; and regulation of cytokinesis. Located in nuclear matrix and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-152670383-TATAGCA-T is Benign according to our data. Variant chr2-152670383-TATAGCA-T is described in ClinVar as [Benign]. Clinvar id is 711346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00591 (901/152360) while in subpopulation AFR AF= 0.0201 (834/41586). AF 95% confidence interval is 0.0189. There are 13 homozygotes in gnomad4. There are 436 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 887 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF40A	NM_001365597.4	c.1606-8_1606-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000545856.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF40A	ENST00000545856.8	c.1606-8_1606-3del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001365597.4	P3

Frequencies

GnomAD3 genomes AF: 0.00583 AC: 887 AN: 152242 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

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: 0.0000882

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00149 AC: 343 AN: 229938 Hom.: 2 AF XY: 0.00121 AC XY: 152 AN XY: 125124

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000375

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000561

Gnomad OTH exome AF: 0.00108

GnomAD4 exome AF: 0.000705 AC: 1021 AN: 1448262 Hom.: 7 AF XY: 0.000618 AC XY: 445 AN XY: 720334

Gnomad4 AFR exome AF: 0.0237

Gnomad4 AMR exome AF: 0.00159

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000719

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000514

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00591 AC: 901 AN: 152360 Hom.: 13 Cov.: 33 AF XY: 0.00585 AC XY: 436 AN XY: 74508

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.00274

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00898

Alfa AF: 0.00339 Hom.: 1

Bravo AF: 0.00684

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113172412; hg19: chr2-153526897;