19-2275080-A-G

Position:

• chr19-2275080-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198532.3(PEAK3):​c.*600T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,762 control chromosomes in the GnomAD database, including 31,784 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.62 (31745 hom., cov: 30)
  • Exomes 𝑓: 0.71 (39 hom.)
• Consequence: PEAK3 NM_198532.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

Genes affected

PEAK3 (HGNC:24793): (PEAK family member 3) Enables protein self-association. Involved in regulation of actin cytoskeleton organization and regulation of cell shape. Predicted to be active in actin cytoskeleton and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000273734 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAK3	NM_198532.3	c.*600T>C		3_prime_UTR_variant	4/4	ENST00000342063.5	NP_940934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEAK3	ENST00000342063	c.*600T>C		3_prime_UTR_variant	4/4	2	NM_198532.3	ENSP00000345102.3
ENSG00000273734	ENST00000621615.1	n.146+5336A>G		intron_variant		2		ENSP00000481965.1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93701 AN: 151490 Hom.: 31744 Cov.: 30

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.886

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.714 AC: 110 AN: 154 Hom.: 39 Cov.: 0 AF XY: 0.704 AC XY: 76 AN XY: 108

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.690

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.618 AC: 93721 AN: 151608 Hom.: 31745 Cov.: 30 AF XY: 0.624 AC XY: 46233 AN XY: 74038

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.736

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.886

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.718

Gnomad4 OTH AF: 0.680

Alfa AF: 0.715 Hom.: 49861

Bravo AF: 0.609

Asia WGS AF: 0.810 AC: 2815 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.26
DANN	Benign	0.20

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: rs2523178; hg19: chr19-2275079;