chr8-27921688-C-T

Position:

chr8-27921688-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173833.6(SCARA5):c.799G>A(p.Val267Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,607,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SCARA5
NM_173833.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.303

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052324474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SCARA5	NM_173833.6 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	4/9	ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1 linkuse as main transcript	c.670G>A	p.Val224Ile	missense_variant	3/8		NP_001400130.1
SCARA5	NM_001413202.1 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	4/7		NP_001400131.1
SCARA5	NM_001413203.1 linkuse as main transcript	c.-6G>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.799G>A	p.Val267Ile	missense_variant	4/9	2	NM_173833.6	ENSP00000346990	P1	Q6ZMJ2-1
SCARA5	ENST00000524352.5 linkuse as main transcript	c.799G>A	p.Val267Ile	missense_variant	4/7	1		ENSP00000428663		Q6ZMJ2-2
SCARA5	ENST00000518030.1 linkuse as main transcript	c.670G>A	p.Val224Ile	missense_variant	2/5	1		ENSP00000430713		Q6ZMJ2-3
SCARA5	ENST00000380385.6 linkuse as main transcript	c.242-11945G>A		intron_variant		1		ENSP00000369746		Q6ZMJ2-4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

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:

0.000479

GnomAD3 exomes

AF:

0.0000427

AC:

AN:

234358

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000518

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000480

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000282

AC:

AN:

1455342

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

723298

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000540

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000666

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

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

Apr 22, 2022

The c.799G>A (p.V267I) 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 799, causing the valine (V) at amino acid position 267 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.37

DANN

Benign

0.86

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.052

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

-0.57

N;N;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.45

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.64

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.094

MutPred

0.33

Loss of MoRF binding (P = 0.125);Loss of MoRF binding (P = 0.125);.;

MVP

0.45

MPC

0.21

ClinPred

0.015

GERP RS

-9.5

Varity_R

0.026

gMVP

0.24

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