chr8-27649777-C-T

Variant names:

• chr8-27649777-C-T
• rs201020809
• NM_016240.3:c.83C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016240.3(SCARA3):​c.83C>T​(p.Pro28Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000805 in 1,613,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: SCARA3 NM_016240.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08178589).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016240.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARA3	NM_016240.3	MANE Select	c.83C>T	p.Pro28Leu	missense	Exon 2 of 6	NP_057324.2
	SCARA3	NM_182826.2		c.83C>T	p.Pro28Leu	missense	Exon 2 of 6	NP_878185.1	Q6AZY7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARA3	ENST00000301904.4	TSL:1 MANE Select	c.83C>T	p.Pro28Leu	missense	Exon 2 of 6	ENSP00000301904.3	Q6AZY7-1
	SCARA3	ENST00000337221.8	TSL:1	c.83C>T	p.Pro28Leu	missense	Exon 2 of 6	ENSP00000337985.3	Q6AZY7-2
	SCARA3	ENST00000890601.1		c.83C>T	p.Pro28Leu	missense	Exon 3 of 7	ENSP00000560660.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 40 AN: 251028 AF XY: 0.000177

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000821 AC: 120 AN: 1461790 Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58 AN XY: 727192

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 71 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111966

Other (OTH) AF: 0.0000828 AC: 5 AN: 60394

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152182 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000718

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)
-	-	1	SCARA3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.082	T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Benign	1.9	L
PhyloP100		3.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.16
Sift	Uncertain	0.020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.92	P
Vest4		0.53
MVP		0.93
MPC		0.39
ClinPred		0.14	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.099
gMVP		0.40
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs201020809; hg19: chr8-27507294;