Variant chr8-27921813-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_173833.6(SCARA5):c.674G>A(p.Gly225Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,551,760 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SCARA5
NM_173833.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

Variant links:

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]

SCARA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCARA5	NM_173833.6 linkuse as main transcript	c.674G>A	p.Gly225Asp	missense_variant	4/9	ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1 linkuse as main transcript	c.545G>A	p.Gly182Asp	missense_variant	3/8		NP_001400130.1
SCARA5	NM_001413202.1 linkuse as main transcript	c.674G>A	p.Gly225Asp	missense_variant	4/7		NP_001400131.1
SCARA5	NM_001413203.1 linkuse as main transcript	c.-131G>A		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 linkuse as main transcript	c.674G>A	p.Gly225Asp	missense_variant	4/9	2	NM_173833.6	ENSP00000346990	P1	Q6ZMJ2-1
SCARA5	ENST00000524352.5 linkuse as main transcript	c.674G>A	p.Gly225Asp	missense_variant	4/7	1		ENSP00000428663		Q6ZMJ2-2
SCARA5	ENST00000518030.1 linkuse as main transcript	c.545G>A	p.Gly182Asp	missense_variant	2/5	1		ENSP00000430713		Q6ZMJ2-3
SCARA5	ENST00000380385.6 linkuse as main transcript	c.242-12070G>A		intron_variant		1		ENSP00000369746		Q6ZMJ2-4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1399520

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

692120

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.674G>A (p.G225D) alteration is located in exon 4 (coding exon 3) of the SCARA5 gene. This alteration results from a G to A substitution at nucleotide position 674, causing the glycine (G) at amino acid position 225 to be replaced by an aspartic acid (D). 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

Benign

0.19

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;.;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

T;T;T

M_CAP

Uncertain

0.28

MetaRNN

Pathogenic

0.79

D;D;D

MetaSVM

Uncertain

0.64

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.94

N;N;N

REVEL

Uncertain

0.64

Sift

Uncertain

0.019

D;T;T

Sift4G

Benign

0.21

T;D;T

Polyphen

1.0

D;D;D

Vest4

0.84

MutPred

0.42

Loss of catalytic residue at V226 (P = 0.1241);Loss of catalytic residue at V226 (P = 0.1241);.;

MVP

0.95

MPC

1.0

ClinPred

0.95

GERP RS

4.9

Varity_R

0.24

gMVP

0.65

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over