1-222650187-A-C

Variant names:

• chr1-222650187-A-C
• rs17465637
• NM_198551.4:c.3632-105A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 199 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 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.3632-105A>C		intron	N/A	NP_940953.2
	MIA3	NM_001324062.2		c.3632-105A>C		intron	N/A	NP_001310991.1
	MIA3	NM_001324063.2		c.3632-105A>C		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.3632-105A>C		intron	N/A	ENSP00000340900.5	Q5JRA6-1
	MIA3	ENST00000340535.11	TSL:1	c.266-105A>C		intron	N/A	ENSP00000345866.7	Q5JRA6-4
	MIA3	ENST00000883516.1		c.3632-105A>C		intron	N/A	ENSP00000553575.1

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

GnomAD2 exomes AF: 0.643 AC: 99728 AN: 155216 AF XY: 0.651

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 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

African (AFR) AF: 0.262 AC: 4148 AN: 15856

American (AMR) AF: 0.498 AC: 16896 AN: 33938

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 14142 AN: 19672

East Asian (EAS) AF: 0.562 AC: 17622 AN: 31364

South Asian (SAS) AF: 0.630 AC: 38967 AN: 61870

European-Finnish (FIN) AF: 0.747 AC: 34982 AN: 46846

Middle Eastern (MID) AF: 0.668 AC: 2679 AN: 4012

European-Non Finnish (NFE) AF: 0.726 AC: 246984 AN: 340324

Other (OTH) AF: 0.660 AC: 20369 AN: 30876

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

African (AFR) AF: 0.257 AC: 10674 AN: 41458

American (AMR) AF: 0.559 AC: 8536 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2482 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3081 AN: 5168

South Asian (SAS) AF: 0.604 AC: 2910 AN: 4818

European-Finnish (FIN) AF: 0.750 AC: 7935 AN: 10582

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49141 AN: 67974

Other (OTH) AF: 0.587 AC: 1236 AN: 2106

Alfa AF: 0.671 Hom.: 150448

Bravo AF: 0.541

Asia WGS AF: 0.545 AC: 1897 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.059
DANN	Benign	0.56
PhyloP100		-0.63
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: rs17465637; hg19: chr1-222823529;