chr8-27921709-G-A

Variant names:

• chr8-27921709-G-A
• rs746653643
• NM_173833.6:c.778C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_173833.6(SCARA5):​c.778C>T​(p.Arg260Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,599,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000070 (0 hom.)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.89
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.747

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.778C>T	p.Arg260Cys	missense	Exon 4 of 9	NP_776194.2
	SCARA5	NM_001413201.1		c.649C>T	p.Arg217Cys	missense	Exon 3 of 8	NP_001400130.1
	SCARA5	NM_001413202.1		c.778C>T	p.Arg260Cys	missense	Exon 4 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.778C>T	p.Arg260Cys	missense	Exon 4 of 9	ENSP00000346990.3	Q6ZMJ2-1
	SCARA5	ENST00000524352.5	TSL:1	c.778C>T	p.Arg260Cys	missense	Exon 4 of 7	ENSP00000428663.1	Q6ZMJ2-2
	SCARA5	ENST00000518030.1	TSL:1	c.649C>T	p.Arg217Cys	missense	Exon 2 of 5	ENSP00000430713.1	Q6ZMJ2-3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152240 Hom.: 0 Cov.: 34

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000130 AC: 28 AN: 215754 AF XY: 0.000145

Gnomad AFR exome AF: 0.000148

Gnomad AMR exome AF: 0.0000317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000954

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000698 AC: 101 AN: 1447194 Hom.: 0 Cov.: 31 AF XY: 0.0000877 AC XY: 63 AN XY: 718568

African (AFR) AF: 0.0000901 AC: 3 AN: 33284

American (AMR) AF: 0.0000468 AC: 2 AN: 42736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25722

East Asian (EAS) AF: 0.00 AC: 0 AN: 39074

South Asian (SAS) AF: 0.000466 AC: 39 AN: 83692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50966

Middle Eastern (MID) AF: 0.000178 AC: 1 AN: 5612

European-Non Finnish (NFE) AF: 0.0000488 AC: 54 AN: 1106322

Other (OTH) AF: 0.0000335 AC: 2 AN: 59786

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152240 Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2 AN XY: 74382

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

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68034

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

Alfa AF: 0.000100 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.000108 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	-0.050
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.33	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N
REVEL	Pathogenic	0.74
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.68
MVP		0.99
MPC		1.0
ClinPred		0.18	T
GERP RS		4.8
Varity_R		0.19
gMVP		0.56
Mutation Taster		=48/52	disease causing

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: rs746653643; hg19: chr8-27779226; COSMIC: COSV57282605;