8-27879749-T-C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

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

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

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=0.03808859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCARA5	NM_173833.6	c.1171A>G	p.Met391Val	missense_variant	Exon 8 of 9	ENST00000354914.8	NP_776194.2
SCARA5	NM_001413201.1	c.1042A>G	p.Met348Val	missense_variant	Exon 7 of 8		NP_001400130.1
SCARA5	NM_001413203.1	c.367A>G	p.Met123Val	missense_variant	Exon 7 of 8		NP_001400132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCARA5	ENST00000354914.8	c.1171A>G	p.Met391Val	missense_variant	Exon 8 of 9	2	NM_173833.6	ENSP00000346990.3
SCARA5	ENST00000380385.6	c.496A>G	p.Met166Val	missense_variant	Exon 7 of 8	1		ENSP00000369746.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1171A>G (p.M391V) alteration is located in exon 8 (coding exon 7) of the SCARA5 gene. This alteration results from a A to G substitution at nucleotide position 1171, causing the methionine (M) at amino acid position 391 to be replaced by a valine (V). 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	0.081
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;T
M_CAP	Benign	0.00066	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.51	N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.35	N;N
REVEL	Benign	0.017
Sift	Benign	0.84	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.0	B;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

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.

Other links and lift over

hg19: chr8-27737266; COSMIC: COSV61574472;