rs28939076

Variant names:

• chr2-189575202-G-C
• NM_014585.6:c.230C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-189575202-G-C
• chr2-189575202-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_014585.6(SLC40A1):​c.230C>G​(p.Ala77Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC40A1 NM_014585.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.07

Genes affected

SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a mutagenesis_site Loss of iron export function. (size 0) in uniprot entity S40A1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC40A1	NM_014585.6	c.230C>G	p.Ala77Gly	missense_variant	Exon 3 of 8	ENST00000261024.7	NP_055400.1
SLC40A1	XM_047444066.1	c.110C>G	p.Ala37Gly	missense_variant	Exon 3 of 8		XP_047300022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000261024.7	c.230C>G	p.Ala77Gly	missense_variant	Exon 3 of 8	1	NM_014585.6	ENSP00000261024.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.052	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Pathogenic	0.71
Sift	Benign	0.032	D;T
Sift4G	Benign	0.12	T;.
Polyphen		1.0	D;.
Vest4		0.77
MutPred		0.52		Loss of stability (P = 0.1055);Loss of stability (P = 0.1055);
MVP		0.43
MPC		1.3
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.71
gMVP		0.76

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: chr2-190439928; COSMIC: COSV53723625; COSMIC: COSV53723625;