dbSNP rs374738537: SCARA5:p.Asp258Tyr (chr8-27921715-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173833.6(SCARA5):c.772G>T(p.Asp258Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SCARA5
NM_173833.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.11

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:

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ACMG classification

Classification made for transcript

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, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA5	NM_173833.6 link	c.772G>T	p.Asp258Tyr	missense_variant	Exon 4 of 9	ENST00000354914.8	NP_776194.2	Q6ZMJ2-1
SCARA5	NM_001413201.1 link	c.643G>T	p.Asp215Tyr	missense_variant	Exon 3 of 8		NP_001400130.1
SCARA5	NM_001413202.1 link	c.772G>T	p.Asp258Tyr	missense_variant	Exon 4 of 7		NP_001400131.1
SCARA5	NM_001413203.1 link	c.-33G>T		5_prime_UTR_variant	Exon 3 of 8		NP_001400132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCARA5	ENST00000354914.8 link	c.772G>T	p.Asp258Tyr	missense_variant	Exon 4 of 9	2	NM_173833.6	ENSP00000346990.3	Q6ZMJ2-1
SCARA5	ENST00000524352.5 link	c.772G>T	p.Asp258Tyr	missense_variant	Exon 4 of 7	1		ENSP00000428663.1	Q6ZMJ2-2
SCARA5	ENST00000518030.1 link	c.643G>T	p.Asp215Tyr	missense_variant	Exon 2 of 5	1		ENSP00000430713.1	Q6ZMJ2-3
SCARA5	ENST00000380385.6 link	c.242-11972G>T		intron_variant	Intron 3 of 7	1		ENSP00000369746.2	Q6ZMJ2-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000471

AC:

AN:

212306

Hom.:

AF XY:

0.00000867

AC XY:

AN XY:

115330

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.92e-7

AC:

AN:

1445098

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

717348

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Pathogenic

0.38

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Uncertain

0.68

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-4.1

D;D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.82

MutPred

0.37

Loss of disorder (P = 0.0227);Loss of disorder (P = 0.0227);.;

MVP

0.98

MPC

1.0

ClinPred

0.99

GERP RS

3.9

Varity_R

0.56

gMVP

0.79

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over