rs3008613

chr1-222622427-G-Achr1-222622427-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198551.4(MIA3):c.267+1135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.957 in 152,290 control chromosomes in the GnomAD database, including 69,793 homozygotes. 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: 𝑓 0.96 (69793 hom., cov: 32)
• Consequence: MIA3 NM_198551.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

Genes affected

MIA3 (HGNC:24008): (MIA SH3 domain ER export factor 3) Enables cargo receptor activity. Involved in several processes, including COPII-coated vesicle cargo loading; cell migration involved in sprouting angiogenesis; and regulation of leukocyte migration. Located in endoplasmic reticulum exit site and endoplasmic reticulum membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIA3	NM_198551.4	c.267+1135G>A		intron_variant		ENST00000344922.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIA3	ENST00000344922.10	c.267+1135G>A		intron_variant		5	NM_198551.4	P1
MIA3	ENST00000470521.1	n.279+1135G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145644 AN: 152172 Hom.: 69732 Cov.: 32

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.965

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

GnomAD4 genome AF: 0.957 AC: 145765 AN: 152290 Hom.: 69793 Cov.: 32 AF XY: 0.956 AC XY: 71170 AN XY: 74444

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.981

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.965

Alfa AF: 0.959 Hom.: 11316

Bravo AF: 0.959

Asia WGS AF: 0.892 AC: 3104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	6.4
Dann	Benign	0.66

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: rs3008613; hg19: chr1-222795769;