19-2275080-A-G

Variant names:

• chr19-2275080-A-G
• rs2523178
• NM_198532.3:c.*600T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEAK3	NM_198532.3	c.*600T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000342063.5	NP_940934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEAK3	ENST00000342063.5	c.*600T>C		3_prime_UTR_variant	Exon 4 of 4	2	NM_198532.3	ENSP00000345102.3
ENSG00000273734	ENST00000621615.1	n.146+5336A>G		intron_variant	Intron 1 of 7	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 6 AN: 6

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.929 AC: 13 AN: 14

European-Finnish (FIN) AF: 0.600 AC: 18 AN: 30

Middle Eastern (MID) AF: 0.500 AC: 2 AN: 4

European-Non Finnish (NFE) AF: 0.690 AC: 58 AN: 84

Other (OTH) AF: 0.813 AC: 13 AN: 16

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

African (AFR) AF: 0.318 AC: 13138 AN: 41302

American (AMR) AF: 0.736 AC: 11217 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2750 AN: 3472

East Asian (EAS) AF: 0.886 AC: 4537 AN: 5122

South Asian (SAS) AF: 0.809 AC: 3895 AN: 4814

European-Finnish (FIN) AF: 0.693 AC: 7285 AN: 10506

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48713 AN: 67842

Other (OTH) AF: 0.680 AC: 1428 AN: 2100

Alfa AF: 0.688 Hom.: 88424

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
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs2523178; hg19: chr19-2275079;