chr8-27921699-C-G

Position:

• chr8-27921699-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173833.6(SCARA5):​c.788G>C​(p.Arg263Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.42

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARA5	NM_173833.6	c.788G>C	p.Arg263Pro	missense_variant	4/9	ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1	c.659G>C	p.Arg220Pro	missense_variant	3/8		NP_001400130.1
SCARA5	NM_001413202.1	c.788G>C	p.Arg263Pro	missense_variant	4/7		NP_001400131.1
SCARA5	NM_001413203.1	c.-17G>C		5_prime_UTR_variant	3/8		NP_001400132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARA5	ENST00000354914.8	c.788G>C	p.Arg263Pro	missense_variant	4/9	2	NM_173833.6	ENSP00000346990	P1
SCARA5	ENST00000524352.5	c.788G>C	p.Arg263Pro	missense_variant	4/7	1		ENSP00000428663
SCARA5	ENST00000518030.1	c.659G>C	p.Arg220Pro	missense_variant	2/5	1		ENSP00000430713
SCARA5	ENST00000380385.6	c.242-11956G>C		intron_variant		1		ENSP00000369746

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 07, 2024

The c.788G>C (p.R263P) alteration is located in exon 4 (coding exon 3) of the SCARA5 gene. This alteration results from a G to C substitution at nucleotide position 788, causing the arginine (R) at amino acid position 263 to be replaced by a proline (P). 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;.;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.21	N;D;D
REVEL	Pathogenic	0.79
Sift	Benign	0.032	D;D;T
Sift4G	Uncertain	0.035	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.55
MutPred		0.70		Loss of MoRF binding (P = 0.0073);Loss of MoRF binding (P = 0.0073);.;
MVP		0.98
MPC		1.1
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.41
gMVP		0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs765044292; hg19: chr8-27779216;