rs17011666

Variant names:

• chr1-222625623-G-A
• rs17011666
• NM_198551.4:c.354+769G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-222625623-G-A
• chr1-222625623-G-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.354+769G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 152,184 control chromosomes in the GnomAD database, including 40,343 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 0.72 (40343 hom., cov: 33)
• Consequence: MIA3 NM_198551.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 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.354+769G>A		intron	N/A	NP_940953.2
	MIA3	NM_001324062.2		c.354+769G>A		intron	N/A	NP_001310991.1
	MIA3	NM_001324063.2		c.354+769G>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.354+769G>A		intron	N/A	ENSP00000340900.5	Q5JRA6-1
	MIA3	ENST00000883516.1		c.354+769G>A		intron	N/A	ENSP00000553575.1
	MIA3	ENST00000929361.1		c.354+769G>A		intron	N/A	ENSP00000599420.1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109950 AN: 152066 Hom.: 40309 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.701

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.723 AC: 110022 AN: 152184 Hom.: 40343 Cov.: 33 AF XY: 0.719 AC XY: 53474 AN XY: 74394

African (AFR) AF: 0.647 AC: 26841 AN: 41498

American (AMR) AF: 0.628 AC: 9611 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2557 AN: 3472

East Asian (EAS) AF: 0.584 AC: 3024 AN: 5174

South Asian (SAS) AF: 0.622 AC: 3004 AN: 4826

European-Finnish (FIN) AF: 0.795 AC: 8412 AN: 10582

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54220 AN: 68014

Other (OTH) AF: 0.694 AC: 1468 AN: 2116

Alfa AF: 0.761 Hom.: 60507

Bravo AF: 0.706

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.80
PhyloP100		-0.34
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: rs17011666; hg19: chr1-222798965; COSMIC: COSV60511260; COSMIC: COSV60511260;