Variant 8-27921934-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173833.6(SCARA5):c.553C>A(p.Leu185Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

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: 1.09

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23106268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCARA5	NM_173833.6 linkuse as main transcript	c.553C>A	p.Leu185Ile	missense_variant	4/9	ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1 linkuse as main transcript	c.424C>A	p.Leu142Ile	missense_variant	3/8		NP_001400130.1
SCARA5	NM_001413202.1 linkuse as main transcript	c.553C>A	p.Leu185Ile	missense_variant	4/7		NP_001400131.1
SCARA5	NM_001413203.1 linkuse as main transcript	c.-252C>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.553C>A	p.Leu185Ile	missense_variant	4/9	2	NM_173833.6	ENSP00000346990	P1	Q6ZMJ2-1
SCARA5	ENST00000524352.5 linkuse as main transcript	c.553C>A	p.Leu185Ile	missense_variant	4/7	1		ENSP00000428663		Q6ZMJ2-2
SCARA5	ENST00000518030.1 linkuse as main transcript	c.424C>A	p.Leu142Ile	missense_variant	2/5	1		ENSP00000430713		Q6ZMJ2-3
SCARA5	ENST00000380385.6 linkuse as main transcript	c.242-12191C>A		intron_variant		1		ENSP00000369746		Q6ZMJ2-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1384692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

684018

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000278

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.24e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000264

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

Mar 18, 2024

The c.553C>A (p.L185I) alteration is located in exon 4 (coding exon 3) of the SCARA5 gene. This alteration results from a C to A substitution at nucleotide position 553, causing the leucine (L) at amino acid position 185 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.68

T;T;T

M_CAP

Pathogenic

0.38

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.8

L;L;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.46

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.99

D;B;B

Vest4

0.18

MutPred

0.39

Loss of disorder (P = 0.0608);Loss of disorder (P = 0.0608);.;

MVP

0.80

MPC

0.28

ClinPred

0.25

GERP RS

3.8

Varity_R

0.059

gMVP

0.11

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