8-27658606-C-G

Variant names:

• chr8-27658606-C-G
• NM_016240.3:c.436C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016240.3(SCARA3):​c.436C>G​(p.Gln146Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCARA3 NM_016240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.89

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA3	NM_016240.3	c.436C>G	p.Gln146Glu	missense_variant	Exon 5 of 6	ENST00000301904.4	NP_057324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARA3	ENST00000301904.4	c.436C>G	p.Gln146Glu	missense_variant	Exon 5 of 6	1	NM_016240.3	ENSP00000301904.3
SCARA3	ENST00000337221.8	c.436C>G	p.Gln146Glu	missense_variant	Exon 5 of 6	1		ENSP00000337985.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 23, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.436C>G (p.Q146E) alteration is located in exon 5 (coding exon 5) of the SCARA3 gene. This alteration results from a C to G substitution at nucleotide position 436, causing the glutamine (Q) at amino acid position 146 to be replaced by a glutamic acid (E). 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	0.10
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.048	.;T
Eigen	Uncertain	0.63
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.16
Sift	Benign	0.13	T;T
Sift4G	Uncertain	0.043	D;D
Polyphen		0.99	D;D
Vest4		0.58
MutPred		0.23		Loss of ubiquitination at K141 (P = 0.1216);Loss of ubiquitination at K141 (P = 0.1216);
MVP		0.93
MPC		0.43
ClinPred		0.54	D
GERP RS		6.0
Varity_R		0.096
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-27516123;