chr8-27879749-T-C

Variant names:

• chr8-27879749-T-C
• NM_173833.6:c.1171A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173833.6(SCARA5):​c.1171A>G​(p.Met391Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.499
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03808859).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARA5	NM_173833.6	MANE Select	c.1171A>G	p.Met391Val	missense	Exon 8 of 9	NP_776194.2
	SCARA5	NM_001413201.1		c.1042A>G	p.Met348Val	missense	Exon 7 of 8	NP_001400130.1
	SCARA5	NM_001413203.1		c.367A>G	p.Met123Val	missense	Exon 7 of 8	NP_001400132.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCARA5	ENST00000354914.8	TSL:2 MANE Select	c.1171A>G	p.Met391Val	missense	Exon 8 of 9	ENSP00000346990.3	Q6ZMJ2-1
	SCARA5	ENST00000380385.6	TSL:1	c.496A>G	p.Met166Val	missense	Exon 7 of 8	ENSP00000369746.2	Q6ZMJ2-4
	SCARA5	ENST00000881549.1		c.1171A>G	p.Met391Val	missense	Exon 9 of 10	ENSP00000551608.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.79
DANN	Benign	0.44
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.51	N
PhyloP100		0.50
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.017
Sift	Benign	0.84	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.088
MutPred		0.39		Loss of disorder (P = 0.1079)
MVP		0.072
MPC		0.26
ClinPred		0.020	T
GERP RS		-8.6
Varity_R		0.047
gMVP		0.29
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr8-27737266; COSMIC: COSV61574472;