chr8-27658739-C-T

Position:

• chr8-27658739-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016240.3(SCARA3):​c.569C>T​(p.Ala190Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 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: 1.85

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 (HGNC:):

ACMG classification

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=0.1504961).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARA3	NM_016240.3	c.569C>T	p.Ala190Val	missense_variant	5/6	ENST00000301904.4	NP_057324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARA3	ENST00000301904.4	c.569C>T	p.Ala190Val	missense_variant	5/6	1	NM_016240.3	ENSP00000301904.3
SCARA3	ENST00000337221.8	c.569C>T	p.Ala190Val	missense_variant	5/6	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2023

The c.569C>T (p.A190V) alteration is located in exon 5 (coding exon 5) of the SCARA3 gene. This alteration results from a C to T substitution at nucleotide position 569, causing the alanine (A) at amino acid position 190 to be replaced by a valine (V). 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	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.041
Sift	Uncertain	0.022	D;D
Sift4G	Benign	0.082	T;D
Polyphen		0.0010	B;B
Vest4		0.13
MutPred		0.32		Gain of MoRF binding (P = 0.2673);Gain of MoRF binding (P = 0.2673);
MVP		0.76
MPC		0.17
ClinPred		0.17	T
GERP RS		4.3
Varity_R		0.10
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr8-27516256;