Genetic Variant SCARA3:p.Leu113Met (chr8-27658507-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_016240.3(SCARA3):c.337C>A(p.Leu113Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000746 in 1,608,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L113V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SCARA3
NM_016240.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.265

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:

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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=0.13194656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA3	NM_016240.3 link	c.337C>A	p.Leu113Met	missense_variant	Exon 5 of 6	ENST00000301904.4	NP_057324.2	Q6AZY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARA3	ENST00000301904.4 link	c.337C>A	p.Leu113Met	missense_variant	Exon 5 of 6	1	NM_016240.3	ENSP00000301904.3		Q6AZY7-1
SCARA3	ENST00000337221.8 link	c.337C>A	p.Leu113Met	missense_variant	Exon 5 of 6	1		ENSP00000337985.3		Q6AZY7-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000814

AC:

AN:

245770

Hom.:

AF XY:

0.00000754

AC XY:

AN XY:

132636

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1455970

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

723988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.28

PROVEAN

Benign

0.14

N;N

REVEL

Benign

0.042

Sift

Benign

0.11

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.25

B;B

Vest4

0.22

MutPred

0.19

Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);

MVP

0.88

MPC

0.38

ClinPred

0.25

GERP RS

5.0

Varity_R

0.067

gMVP

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over