19-2276372-C-G

Variant names:

• chr19-2276372-C-G
• rs557687551
• NM_198532.3:c.730G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198532.3(PEAK3):​c.730G>C​(p.Gly244Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,599,420 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PEAK3 NM_198532.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06763899).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEAK3	NM_198532.3	c.730G>C	p.Gly244Arg	missense_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.730G>C	p.Gly244Arg	missense_variant	Exon 4 of 4	2	NM_198532.3	ENSP00000345102.3
ENSG00000273734	ENST00000621615.1	n.146+6628C>G		intron_variant	Intron 1 of 7	2		ENSP00000481965.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447244 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720330

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74334

Gnomad4 AFR AF: 0.0000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.7
DANN	Benign	0.94
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.99	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.016
Sift	Benign	0.22	T
Sift4G	Benign	0.11	T
Polyphen		0.36	B
Vest4		0.062
MutPred		0.33		Loss of relative solvent accessibility (P = 0.0676);
MVP		0.34
MPC		0.33
ClinPred		0.13	T
GERP RS		3.0
Varity_R		0.050
gMVP		0.37

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: rs557687551; hg19: chr19-2276371;