dbSNP rs763964092: SCARA5:p.Val267Leu (chr8-27921688-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 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

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=0.110723644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA5	NM_173833.6 link	c.799G>T	p.Val267Leu	missense_variant	Exon 4 of 9	ENST00000354914.8	NP_776194.2	Q6ZMJ2-1
SCARA5	NM_001413201.1 link	c.670G>T	p.Val224Leu	missense_variant	Exon 3 of 8		NP_001400130.1
SCARA5	NM_001413202.1 link	c.799G>T	p.Val267Leu	missense_variant	Exon 4 of 7		NP_001400131.1
SCARA5	NM_001413203.1 link	c.-6G>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.799G>T	p.Val267Leu	missense_variant	Exon 4 of 9	2	NM_173833.6	ENSP00000346990.3	Q6ZMJ2-1
SCARA5	ENST00000524352.5 link	c.799G>T	p.Val267Leu	missense_variant	Exon 4 of 7	1		ENSP00000428663.1	Q6ZMJ2-2
SCARA5	ENST00000518030.1 link	c.670G>T	p.Val224Leu	missense_variant	Exon 2 of 5	1		ENSP00000430713.1	Q6ZMJ2-3
SCARA5	ENST00000380385.6 link	c.242-11945G>T		intron_variant	Intron 3 of 7	1		ENSP00000369746.2	Q6ZMJ2-4

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

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:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

1.1

DANN

Benign

0.79

DEOGEN2

Benign

0.024

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.67

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.35

N;N;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.96

N;N;N

REVEL

Benign

0.21

Sift

Benign

0.52

T;T;T

Sift4G

Benign

0.34

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.082

MutPred

0.36

Gain of helix (P = 0.0854);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

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over