12-47779569-T-A

Position:

• chr12-47779569-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017842.3(SLC48A1):​c.304+374T>A variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC48A1 NM_017842.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

Genes affected

SLC48A1 (HGNC:26035): (solute carrier family 48 member 1) Enables heme binding activity and heme transmembrane transporter activity. Involved in heme transport. Located in endosome membrane; lysosomal membrane; and 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 (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC48A1	NM_017842.3	c.304+374T>A		intron_variant		ENST00000442218.3
SLC48A1	XM_005269016.4	c.385+374T>A		intron_variant
SLC48A1	XM_017019617.3	c.304+374T>A		intron_variant
SLC48A1	XM_047429134.1	c.418+374T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC48A1	ENST00000442218.3	c.304+374T>A		intron_variant		1	NM_017842.3	P1
SLC48A1	ENST00000442892.2	c.133+374T>A		intron_variant		1
SLC48A1	ENST00000547002.5	c.133+374T>A		intron_variant		3
SLC48A1	ENST00000551301.1	c.*141+374T>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.80

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: rs4760636; hg19: chr12-48173352;