3-52212014-G-C

Variant names:

• chr3-52212014-G-C
• rs9813468
• NM_000688.6:c.1600-244G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000688.6(ALAS1):​c.1600-244G>C 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: 32)
• Consequence: ALAS1 NM_000688.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.57
• Publications: 2 publications found

Genes affected

ALAS1 (HGNC:396): (5'-aminolevulinate synthase 1) This gene encodes the mitochondrial enzyme which is catalyzes the rate-limiting step in heme (iron-protoporphyrin) biosynthesis. The enzyme encoded by this gene is the housekeeping enzyme; a separate gene encodes a form of the enzyme that is specific for erythroid tissue. The level of the mature encoded protein is regulated by heme: high levels of heme down-regulate the mature enzyme in mitochondria while low heme levels up-regulate. A pseudogene of this gene is located on chromosome 12. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

ENSG00000296921 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000688.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALAS1	NM_000688.6	MANE Select	c.1600-244G>C		intron	N/A	NP_000679.1
	ALAS1	NM_001304444.1		c.1651-244G>C		intron	N/A	NP_001291373.1
	ALAS1	NM_001304443.1		c.1600-244G>C		intron	N/A	NP_001291372.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALAS1	ENST00000484952.6	TSL:1 MANE Select	c.1600-244G>C		intron	N/A	ENSP00000418779.1
	ALAS1	ENST00000310271.6	TSL:1	c.1600-244G>C		intron	N/A	ENSP00000309259.2
	ALAS1	ENST00000469224.5	TSL:1	c.1600-244G>C		intron	N/A	ENSP00000417719.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.055
DANN	Benign	0.35
PhyloP100		-3.6

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

Other links and lift over

dbSNP: rs9813468; hg19: chr3-52246030;