8-27921688-C-T

Variant names:

• chr8-27921688-C-T
• rs763964092
• NM_173833.6:c.799G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173833.6(SCARA5):​c.799G>A​(p.Val267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,607,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.303
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052324474).

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.799G>A	p.Val267Ile	missense	Exon 4 of 9	NP_776194.2
	SCARA5	NM_001413201.1		c.670G>A	p.Val224Ile	missense	Exon 3 of 8	NP_001400130.1
	SCARA5	NM_001413202.1		c.799G>A	p.Val267Ile	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.799G>A	p.Val267Ile	missense	Exon 4 of 9	ENSP00000346990.3	Q6ZMJ2-1
	SCARA5	ENST00000524352.5	TSL:1	c.799G>A	p.Val267Ile	missense	Exon 4 of 7	ENSP00000428663.1	Q6ZMJ2-2
	SCARA5	ENST00000518030.1	TSL:1	c.670G>A	p.Val224Ile	missense	Exon 2 of 5	ENSP00000430713.1	Q6ZMJ2-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000427 AC: 10 AN: 234358 AF XY: 0.0000314

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000518

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000480

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000282 AC: 41 AN: 1455342 Hom.: 0 Cov.: 31 AF XY: 0.0000263 AC XY: 19 AN XY: 723298

African (AFR) AF: 0.0000300 AC: 1 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44076

Ashkenazi Jewish (ASJ) AF: 0.000540 AC: 14 AN: 25916

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00 AC: 0 AN: 84898

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52348

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5650

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1109486

Other (OTH) AF: 0.0000666 AC: 4 AN: 60086

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152256 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74386

African (AFR) AF: 0.00 AC: 0 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

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: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000330 AC: 4

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	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.37
DANN	Benign	0.86
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	-0.57	N
PhyloP100		-0.30
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.25
Sift	Benign	0.64	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.094
MutPred		0.33		Loss of MoRF binding (P = 0.125)
MVP		0.45
MPC		0.21
ClinPred		0.015	T
GERP RS		-9.5
Varity_R		0.026
gMVP		0.24
Mutation Taster		=98/2	polymorphism

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: rs763964092; hg19: chr8-27779205; COSMIC: COSV57277824;