8-27921823-C-A

Variant names:

Variant summary

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

The NM_173833.6(SCARA5):c.664G>T(p.Asp222Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,547,332 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 0.000092 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SCARA5
NM_173833.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA5	NM_173833.6 link	c.664G>T	p.Asp222Tyr	missense_variant	Exon 4 of 9	ENST00000354914.8	NP_776194.2	Q6ZMJ2-1
SCARA5	NM_001413201.1 link	c.535G>T	p.Asp179Tyr	missense_variant	Exon 3 of 8		NP_001400130.1
SCARA5	NM_001413202.1 link	c.664G>T	p.Asp222Tyr	missense_variant	Exon 4 of 7		NP_001400131.1
SCARA5	NM_001413203.1 link	c.-141G>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.664G>T	p.Asp222Tyr	missense_variant	Exon 4 of 9	2	NM_173833.6	ENSP00000346990.3	Q6ZMJ2-1
SCARA5	ENST00000524352.5 link	c.664G>T	p.Asp222Tyr	missense_variant	Exon 4 of 7	1		ENSP00000428663.1	Q6ZMJ2-2
SCARA5	ENST00000518030.1 link	c.535G>T	p.Asp179Tyr	missense_variant	Exon 2 of 5	1		ENSP00000430713.1	Q6ZMJ2-3
SCARA5	ENST00000380385.6 link	c.242-12080G>T		intron_variant	Intron 3 of 7	1		ENSP00000369746.2	Q6ZMJ2-4

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000686

AC:

AN:

145816

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80048

show subpopulations

Gnomad AFR exome

AF:

0.000137

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1395132

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689560

show subpopulations

Gnomad4 AFR exome

AF:

0.0000638

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000338

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000159

ESP6500AA

AF:

0.000472

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000881

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.664G>T (p.D222Y) alteration is located in exon 4 (coding exon 3) of the SCARA5 gene. This alteration results from a G to T substitution at nucleotide position 664, causing the aspartic acid (D) at amino acid position 222 to be replaced by a tyrosine (Y). 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

Uncertain

0.45

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.81

T;T;T

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Pathogenic

0.97

MutationAssessor

Benign

1.6

L;L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Pathogenic

0.69

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.57

MVP

0.98

MPC

0.92

ClinPred

0.78

GERP RS

4.9

Varity_R

0.43

gMVP

0.58

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