Variant chr8-27634204-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016240.3(SCARA3):c.4A>C(p.Lys2Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000309 in 1,392,314 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SCARA3
NM_016240.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Variant links:

Genes affected

SCARA3 (HGNC:19000): (scavenger receptor class A member 3) This gene encodes a macrophage scavenger receptor-like protein. This protein has been shown to deplete reactive oxygen species, and thus play an important role in protecting cells from oxidative stress. The expression of this gene is induced by oxidative stress. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

SCARA3 links:

SCARA3 (HGNC:):

SCARA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3582384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARA3	NM_016240.3 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/6	ENST00000301904.4	NP_057324.2	Q6AZY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARA3	ENST00000301904.4 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/6	1	NM_016240.3	ENSP00000301904.3		Q6AZY7-1
SCARA3	ENST00000337221.8 linkuse as main transcript	c.4A>C	p.Lys2Gln	missense_variant	1/6	1		ENSP00000337985.3		Q6AZY7-2

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

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:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000300

AC:

AN:

100022

Hom.:

AF XY:

0.0000345

AC XY:

AN XY:

57952

show subpopulations

Gnomad AFR exome

AF:

0.000301

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000145

AC:

AN:

1240262

Hom.:

Cov.:

AF XY:

0.0000164

AC XY:

AN XY:

608822

show subpopulations

Gnomad4 AFR exome

AF:

0.000545

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.92e-7

Gnomad4 OTH exome

AF:

0.0000604

GnomAD4 genome

AF:

0.000164

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.000531

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:

0.0000147

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000300

AC:

ESP6500EA

AF:

0.000142

AC:

ExAC

AF:

0.0000350

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 07, 2024

The c.4A>C (p.K2Q) alteration is located in exon 1 (coding exon 1) of the SCARA3 gene. This alteration results from a A to C substitution at nucleotide position 4, causing the lysine (K) at amino acid position 2 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.018

.;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.52

T;T

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.36

T;T

MetaSVM

Uncertain

-0.045

MutationAssessor

Benign

0.69

N;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.12

Sift

Benign

0.28

T;T

Sift4G

Benign

0.22

T;D

Polyphen

0.99

D;D

Vest4

0.32

MVP

0.94

MPC

0.18

ClinPred

0.087

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.13

gMVP

0.23

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