1-222622427-G-A

Variant names:

• chr1-222622427-G-A
• rs3008613
• NM_198551.4:c.267+1135G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.968 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIA3	NM_198551.4	MANE Select	c.267+1135G>A		intron	N/A	NP_940953.2
	MIA3	NM_001324062.2		c.267+1135G>A		intron	N/A	NP_001310991.1
	MIA3	NM_001324063.2		c.267+1135G>A		intron	N/A	NP_001310992.1	Q5JRA6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIA3	ENST00000344922.10	TSL:5 MANE Select	c.267+1135G>A		intron	N/A	ENSP00000340900.5	Q5JRA6-1
	MIA3	ENST00000883516.1		c.267+1135G>A		intron	N/A	ENSP00000553575.1
	MIA3	ENST00000929361.1		c.267+1135G>A		intron	N/A	ENSP00000599420.1

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

African (AFR) AF: 0.944 AC: 39206 AN: 41552

American (AMR) AF: 0.981 AC: 15006 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3188 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4567 AN: 5170

South Asian (SAS) AF: 0.888 AC: 4287 AN: 4828

European-Finnish (FIN) AF: 0.964 AC: 10232 AN: 10618

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.971 AC: 66052 AN: 68034

Other (OTH) AF: 0.965 AC: 2036 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.66
PhyloP100		0.16
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: rs3008613; hg19: chr1-222795769;