9-113157790-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001860.3(SLC31A2):c.70G>A(p.Ala24Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC31A2 NM_001860.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.176

Genes affected

SLC31A2 (HGNC:11017): (solute carrier family 31 member 2) Predicted to enable copper ion transmembrane transporter activity. Predicted to be involved in cellular copper ion homeostasis. Predicted to act upstream of or within regulation of copper ion transmembrane transport. Predicted to be located in membrane. Predicted to be active in 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=0.1447322).
• BP6: Variant 9-113157790-G-A is Benign according to our data. Variant chr9-113157790-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2323951.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC31A2	NM_001860.3	c.70G>A	p.Ala24Thr	missense_variant	2/4	ENST00000259392.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC31A2	ENST00000259392.8	c.70G>A	p.Ala24Thr	missense_variant	2/4	1	NM_001860.3	P1
SLC31A2	ENST00000374220.3	c.70G>A	p.Ala24Thr	missense_variant, NMD_transcript_variant	2/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 08, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	8.4
Dann	Benign	0.95
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
MutationTaster	Benign	0.94	D
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.12
Sift	Benign	0.46	T
Sift4G	Benign	0.36	T
Polyphen		0.033	B
Vest4		0.20
MutPred		0.49		Gain of sheet (P = 0.0827);
MVP		0.58
MPC		0.20
ClinPred		0.14	T
GERP RS		-1.6
Varity_R		0.044
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs1829952902; hg19: chr9-115920070;