8-27907235-C-A

Variant names:

• chr8-27907235-C-A
• rs764145315
• NM_173833.6:c.1009G>T

Variant summary

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

The NM_173833.6(SCARA5):​c.1009G>T​(p.Glu337*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCARA5 NM_173833.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.42
• Publications: 0 publications found

Genes affected

SCARA5 (HGNC:28701): (scavenger receptor class A member 5) Predicted to enable ferritin receptor activity. Predicted to be involved in several processes, including cellular iron ion homeostasis; iron ion transmembrane transport; and protein homotrimerization. Predicted to act upstream of or within cellular response to heat. Predicted to be located in cell surface. Predicted to be integral component of plasma membrane. Predicted to be active in external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000253397 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173833.6. 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
	SCARA5	NM_173833.6	MANE Select	c.1009G>T	p.Glu337*	stop_gained	Exon 6 of 9	NP_776194.2
	SCARA5	NM_001413201.1		c.880G>T	p.Glu294*	stop_gained	Exon 5 of 8	NP_001400130.1
	SCARA5	NM_001413202.1		c.1009G>T	p.Glu337*	stop_gained	Exon 6 of 7	NP_001400131.1	Q6ZMJ2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARA5	ENST00000354914.8	TSL:2 MANE Select	c.1009G>T	p.Glu337*	stop_gained	Exon 6 of 9	ENSP00000346990.3	Q6ZMJ2-1
	SCARA5	ENST00000524352.5	TSL:1	c.1009G>T	p.Glu337*	stop_gained	Exon 6 of 7	ENSP00000428663.1	Q6ZMJ2-2
	SCARA5	ENST00000518030.1	TSL:1	c.880G>T	p.Glu294*	stop_gained	Exon 4 of 5	ENSP00000430713.1	Q6ZMJ2-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460818 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726684

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.0000224 AC: 1 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111402

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	48
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Uncertain	0.89	D
PhyloP100		4.4
Vest4		0.87
GERP RS		5.9
Mutation Taster		=12/188	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs764145315; hg19: chr8-27764752;