chr8-27658499-C-T

Variant names:

• chr8-27658499-C-T
• rs772611166
• NM_016240.3:c.329C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_016240.3(SCARA3):​c.329C>T​(p.Pro110Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,598,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: SCARA3 NM_016240.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.375
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06338987).
• BP6: Variant 8-27658499-C-T is Benign according to our data. Variant chr8-27658499-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2462704.Status of the report is criteria_provided_single_submitter, 1 stars.

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.329C>T	p.Pro110Leu	missense	Exon 5 of 6	NP_057324.2
	SCARA3	NM_182826.2		c.329C>T	p.Pro110Leu	missense	Exon 5 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.329C>T	p.Pro110Leu	missense	Exon 5 of 6	ENSP00000301904.3	Q6AZY7-1
	SCARA3	ENST00000337221.8	TSL:1	c.329C>T	p.Pro110Leu	missense	Exon 5 of 6	ENSP00000337985.3	Q6AZY7-2
	SCARA3	ENST00000890601.1		c.329C>T	p.Pro110Leu	missense	Exon 6 of 7	ENSP00000560660.1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152154 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000716 AC: 17 AN: 237430 AF XY: 0.0000860

Gnomad AFR exome AF: 0.000124

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: 0.000111

Gnomad OTH exome AF: 0.000175

GnomAD4 exome AF: 0.0000768 AC: 111 AN: 1446236 Hom.: 0 Cov.: 31 AF XY: 0.0000863 AC XY: 62 AN XY: 718518

African (AFR) AF: 0.000183 AC: 6 AN: 32860

American (AMR) AF: 0.00 AC: 0 AN: 42176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24852

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.0000361 AC: 3 AN: 83094

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52872

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5660

European-Non Finnish (NFE) AF: 0.0000896 AC: 99 AN: 1105374

Other (OTH) AF: 0.0000167 AC: 1 AN: 59702

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152154 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5 AN XY: 74322

African (AFR) AF: 0.0000724 AC: 3 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68032

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

Alfa AF: 0.000221 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000906 AC: 11

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	4.9
DANN	Benign	0.31
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-1.5	N
PhyloP100		0.38
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.040
Sift	Benign	0.50	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.065
MVP		0.88
MPC		0.17
ClinPred		0.0099	T
GERP RS		-0.16
Varity_R		0.017
gMVP		0.093
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs772611166; hg19: chr8-27516016; COSMIC: COSV57269955;