chr8-27907162-A-C

Position:

• chr8-27907162-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173833.6(SCARA5):​c.1082T>G​(p.Met361Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCARA5 NM_173833.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCARA5	NM_173833.6	c.1082T>G	p.Met361Arg	missense_variant	6/9	ENST00000354914.8	NP_776194.2
LOC105379342	XR_949613.4	n.207-1828A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCARA5	ENST00000354914.8	c.1082T>G	p.Met361Arg	missense_variant	6/9	2	NM_173833.6	ENSP00000346990	P1
	ENST00000517735.1	n.164-1828A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2023

The c.1082T>G (p.M361R) alteration is located in exon 6 (coding exon 5) of the SCARA5 gene. This alteration results from a T to G substitution at nucleotide position 1082, causing the methionine (M) at amino acid position 361 to be replaced by an arginine (R). 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	0.28
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.89
DEOGEN2	Benign	0.33	T;.;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	0.055	N;.;N;.
MutationTaster	Benign	0.77	D;D;D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.83	T;T;T;D
Sift4G	Benign	0.37	T;T;T;T
Polyphen		0.29	B;B;B;B
Vest4		0.62
MutPred		0.47		Gain of MoRF binding (P = 0.0349);.;Gain of MoRF binding (P = 0.0349);.;
MVP		0.84
MPC		0.75
ClinPred		0.66	D
GERP RS		5.9
Varity_R		0.67
gMVP		0.50

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: chr8-27764679;