Variant 19-2276414-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198532.3(PEAK3):c.688C>A(p.Leu230Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000901 in 1,597,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

PEAK3
NM_198532.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.104

Variant links:

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]

PEAK3 links:

ENSG00000273734 (HGNC:):

ENSG00000273734 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.082895815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEAK3	NM_198532.3 linkuse as main transcript	c.688C>A	p.Leu230Met	missense_variant	4/4	ENST00000342063.5	NP_940934.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEAK3	ENST00000342063.5 linkuse as main transcript	c.688C>A	p.Leu230Met	missense_variant	4/4	2	NM_198532.3	ENSP00000345102.3		Q6ZS72
ENSG00000273734	ENST00000621615.1 linkuse as main transcript	n.146+6670G>T		intron_variant		2		ENSP00000481965.1		A0A087WYN8

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000489

AC:

AN:

224856

Hom.:

AF XY:

0.0000320

AC XY:

AN XY:

124870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000155

Gnomad NFE exome

AF:

0.0000682

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000872

AC:

126

AN:

1445362

Hom.:

Cov.:

AF XY:

0.0000821

AC XY:

AN XY:

718830

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000120

Gnomad4 NFE exome

AF:

0.0000992

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.000118

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000117

Hom.:

Bravo

AF:

0.000212

ExAC

AF:

0.0000591

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2021

The c.688C>A (p.L230M) alteration is located in exon 4 (coding exon 3) of the C19orf35 gene. This alteration results from a C to A substitution at nucleotide position 688, causing the leucine (L) at amino acid position 230 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.38

M_CAP

Benign

0.0042

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.2

REVEL

Benign

0.031

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.035

Polyphen

0.90

Vest4

0.22

MutPred

0.37

Gain of catalytic residue at L230 (P = 0.0803);

MVP

0.23

MPC

0.50

ClinPred

0.14

GERP RS

0.36

Varity_R

0.26

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over