1-222666496-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

MIA3 Gene-Disease associations (from GenCC):

• odontochondrodysplasia 2 with hearing loss and diabetes

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198551.4. 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
	MIA3	NM_198551.4	MANE Select	c.*877A>G		3_prime_UTR	Exon 28 of 28	NP_940953.2
	MIA3	NM_001324062.2		c.*877A>G		3_prime_UTR	Exon 29 of 29	NP_001310991.1
	MIA3	NM_001324063.2		c.*877A>G		3_prime_UTR	Exon 26 of 26	NP_001310992.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIA3	ENST00000344922.10	TSL:5 MANE Select	c.*877A>G		3_prime_UTR	Exon 28 of 28	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.440 AC: 18173 AN: 41330

American (AMR) AF: 0.883 AC: 13502 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.893 AC: 3098 AN: 3470

East Asian (EAS) AF: 0.867 AC: 4496 AN: 5184

South Asian (SAS) AF: 0.848 AC: 4086 AN: 4820

European-Finnish (FIN) AF: 0.926 AC: 9772 AN: 10558

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.884 AC: 60111 AN: 67996

Other (OTH) AF: 0.809 AC: 1706 AN: 2108

Alfa AF: 0.848 Hom.: 212058

Bravo AF: 0.747

Asia WGS AF: 0.831 AC: 2891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.32
DANN	Benign	0.82
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1053316; hg19: chr1-222839838;