1-222650187-A-C

Position:

• chr1-222650187-A-C

Variant summary

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

The NM_198551.4(MIA3):​c.3632-105A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 736,816 control chromosomes in the GnomAD database, including 165,801 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 0.57 (28044 hom., cov: 32)
  • Exomes 𝑓: 0.68 (137757 hom.)
• Consequence: MIA3 NM_198551.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIA3	NM_198551.4	c.3632-105A>C		intron_variant		ENST00000344922.10	NP_940953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIA3	ENST00000344922.10	c.3632-105A>C		intron_variant		5	NM_198551.4	ENSP00000340900	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86881 AN: 151940 Hom.: 28034 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.586

GnomAD3 exomes AF: 0.643 AC: 99728 AN: 155216 Hom.: 33331 AF XY: 0.651 AC XY: 53444 AN XY: 82086

Gnomad AFR exome AF: 0.249

Gnomad AMR exome AF: 0.496

Gnomad ASJ exome AF: 0.717

Gnomad EAS exome AF: 0.596

Gnomad SAS exome AF: 0.624

Gnomad FIN exome AF: 0.748

Gnomad NFE exome AF: 0.725

Gnomad OTH exome AF: 0.658

GnomAD4 exome AF: 0.679 AC: 396789 AN: 584758 Hom.: 137757 Cov.: 7 AF XY: 0.681 AC XY: 214251 AN XY: 314462

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.719

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.630

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.726

Gnomad4 OTH exome AF: 0.660

GnomAD4 genome AF: 0.571 AC: 86897 AN: 152058 Hom.: 28044 Cov.: 32 AF XY: 0.573 AC XY: 42603 AN XY: 74356

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.587

Alfa AF: 0.695 Hom.: 73119

Bravo AF: 0.541

Asia WGS AF: 0.545 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.059
DANN	Benign	0.56

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: rs17465637; hg19: chr1-222823529;