Genetic Variant SCARA5:p.Val267Leu (chr8-27921688-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173833.6(SCARA5):c.799G>T(p.Val267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,455,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V267I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SCARA5
NM_173833.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.303

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.110723644).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173833.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCARA5	NM_173833.6	MANE Select	c.799G>T	p.Val267Leu	missense	Exon 4 of 9	NP_776194.2
SCARA5	NM_001413201.1		c.670G>T	p.Val224Leu	missense	Exon 3 of 8	NP_001400130.1
SCARA5	NM_001413202.1		c.799G>T	p.Val267Leu	missense	Exon 4 of 7	NP_001400131.1	Q6ZMJ2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCARA5	ENST00000354914.8	TSL:2 MANE Select	c.799G>T	p.Val267Leu	missense	Exon 4 of 9	ENSP00000346990.3	Q6ZMJ2-1
SCARA5	ENST00000524352.5	TSL:1	c.799G>T	p.Val267Leu	missense	Exon 4 of 7	ENSP00000428663.1	Q6ZMJ2-2
SCARA5	ENST00000518030.1	TSL:1	c.670G>T	p.Val224Leu	missense	Exon 2 of 5	ENSP00000430713.1	Q6ZMJ2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1455342

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723298

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33382

American (AMR)

AF:

0.00

AC:

AN:

44076

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25916

East Asian (EAS)

AF:

0.00

AC:

AN:

39500

South Asian (SAS)

AF:

0.00

AC:

AN:

84898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109486

Other (OTH)

AF:

0.00

AC:

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.1

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.024

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.67

M_CAP

Benign

0.025

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.35

PhyloP100

-0.30

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.96

REVEL

Benign

0.21

Sift

Benign

0.52

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.082

MutPred

0.36

Gain of helix (P = 0.0854)

MVP

0.44

MPC

0.25

ClinPred

0.026

GERP RS

-9.5

Varity_R

0.055

gMVP

0.36

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over