1-222666496-A-G

Variant names:

• chr1-222666496-A-G
• rs1053316
• NM_198551.4:c.*877A>G

Variant summary

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

The NM_198551.4(MIA3):​c.*877A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 151,958 control chromosomes in the GnomAD database, including 47,409 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 0.76 (47409 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: MIA3 NM_198551.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA3	NM_198551.4	c.*877A>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000344922.10	NP_940953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIA3	ENST00000344922.10	c.*877A>G		3_prime_UTR_variant	Exon 28 of 28	5	NM_198551.4	ENSP00000340900.5

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116033 AN: 151840 Hom.: 47390 Cov.: 30

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.893

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.808

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.764 AC: 116076 AN: 151958 Hom.: 47409 Cov.: 30 AF XY: 0.770 AC XY: 57182 AN XY: 74304

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.893

Gnomad4 EAS AF: 0.867

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.926

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.809

Alfa AF: 0.868 Hom.: 92256

Bravo AF: 0.747

Asia WGS AF: 0.831 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.82

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: rs1053316; hg19: chr1-222839838;