NM_016240.3:c.359A>T

Variant names:

• chr8-27658529-A-T
• rs138620851
• NM_016240.3:c.359A>T

Variant summary

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

The NM_016240.3(SCARA3):​c.359A>T​(p.His120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H120R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCARA3 NM_016240.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• 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 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.359A>T	p.His120Leu	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.359A>T	p.His120Leu	missense_variant	Exon 5 of 6	1	NM_016240.3	ENSP00000301904.3
SCARA3	ENST00000337221.8	c.359A>T	p.His120Leu	missense_variant	Exon 5 of 6	1		ENSP00000337985.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459944 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726204

African (AFR) AF: 0.0000299 AC: 1 AN: 33418

American (AMR) AF: 0.00 AC: 0 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25952

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 85838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53346

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111240

Other (OTH) AF: 0.00 AC: 0 AN: 60284

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.015	.;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.87	L;L
PhyloP100		1.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.14
Sift	Benign	0.82	T;T
Sift4G	Benign	0.48	T;T
Polyphen		0.0	B;B
Vest4		0.24
MutPred		0.21		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.91
MPC		0.20
ClinPred		0.13	T
GERP RS		3.5
Varity_R		0.063
gMVP		0.25
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs138620851; hg19: chr8-27516046;