8-27907181-C-T

Variant names:

• chr8-27907181-C-T
• rs370541085
• NM_173833.6:c.1063G>A

Variant summary

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

The NM_173833.6(SCARA5):​c.1063G>A​(p.Ala355Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A355S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• 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]

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.1063G>A	p.Ala355Thr	missense	Exon 6 of 9	NP_776194.2
	SCARA5	NM_001413201.1		c.934G>A	p.Ala312Thr	missense	Exon 5 of 8	NP_001400130.1
	SCARA5	NM_001413202.1		c.1063G>A	p.Ala355Thr	missense	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.1063G>A	p.Ala355Thr	missense	Exon 6 of 9	ENSP00000346990.3	Q6ZMJ2-1
	SCARA5	ENST00000524352.5	TSL:1	c.1063G>A	p.Ala355Thr	missense	Exon 6 of 7	ENSP00000428663.1	Q6ZMJ2-2
	SCARA5	ENST00000518030.1	TSL:1	c.934G>A	p.Ala312Thr	missense	Exon 4 of 5	ENSP00000430713.1	Q6ZMJ2-3

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152116 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250738 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461006 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 726820

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111502

Other (OTH) AF: 0.0000166 AC: 1 AN: 60370

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152116 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

African (AFR) AF: 0.0000483 AC: 2 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15278

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000123 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	0.99	L
PhyloP100		1.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.27
Sift	Benign	0.42	T
Sift4G	Benign	0.55	T
Polyphen		0.97	D
Vest4		0.37
MVP		0.93
MPC		0.52
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.17
Mutation Taster		=83/17	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: rs370541085; hg19: chr8-27764698; COSMIC: COSV57277980; COSMIC: COSV57277980;