8-27651510-C-T

Variant names:

• chr8-27651510-C-T
• rs757365316
• NM_016240.3:c.109C>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.109C>T​(p.Arg37Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,611,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SCARA3 NM_016240.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.406
• 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=0.17095402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA3	NM_016240.3	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 3 of 6	ENST00000301904.4	NP_057324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARA3	ENST00000301904.4	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 3 of 6	1	NM_016240.3	ENSP00000301904.3
SCARA3	ENST00000337221.8	c.109C>T	p.Arg37Trp	missense_variant, splice_region_variant	Exon 3 of 6	1		ENSP00000337985.3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 249462 AF XY: 0.0000222

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1459384 Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11 AN XY: 726080

African (AFR) AF: 0.000149 AC: 5 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5062

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111924

Other (OTH) AF: 0.0000166 AC: 1 AN: 60280

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152250 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74386

African (AFR) AF: 0.0000723 AC: 3 AN: 41468

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.109C>T (p.R37W) alteration is located in exon 3 (coding exon 3) of the SCARA3 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the arginine (R) at amino acid position 37 to be replaced by a tryptophan (W). 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	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	.;T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.2	L;L
PhyloP100		0.41
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.2	D;N
REVEL	Benign	0.11
Sift	Benign	0.047	D;D
Sift4G	Benign	0.12	T;T
Polyphen		0.015	B;B
Vest4		0.42
MutPred		0.32		Loss of disorder (P = 0.0028);Loss of disorder (P = 0.0028);
MVP		0.88
MPC		0.17
ClinPred		0.37	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.065
gMVP		0.32
Mutation Taster		=80/20	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: rs757365316; hg19: chr8-27509027;