rs3008621

Variant names:

• chr1-222630704-G-A
• rs3008621
• NM_198551.4:c.3169+315G>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.3169+315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,250 control chromosomes in the GnomAD database, including 1,050 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 0.11 (1050 hom., cov: 32)
• Consequence: MIA3 NM_198551.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.378
• Publications: 19 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA3	NM_198551.4	c.3169+315G>A		intron_variant	Intron 4 of 27	ENST00000344922.10	NP_940953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIA3	ENST00000344922.10	c.3169+315G>A		intron_variant	Intron 4 of 27	5	NM_198551.4	ENSP00000340900.5
MIA3	ENST00000354906.7	c.1915+315G>A		intron_variant	Intron 1 of 12	5		ENSP00000355062.3
MIA3	ENST00000470521.1	n.3181+315G>A		intron_variant	Intron 4 of 6	5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16057 AN: 152130 Hom.: 1050 Cov.: 32

Gnomad AFR AF: 0.0480

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0987

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.105 AC: 16057 AN: 152250 Hom.: 1050 Cov.: 32 AF XY: 0.105 AC XY: 7813 AN XY: 74440

African (AFR) AF: 0.0479 AC: 1989 AN: 41552

American (AMR) AF: 0.0927 AC: 1417 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3472

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5190

South Asian (SAS) AF: 0.0996 AC: 480 AN: 4820

European-Finnish (FIN) AF: 0.159 AC: 1684 AN: 10602

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.139 AC: 9479 AN: 68006

Other (OTH) AF: 0.125 AC: 264 AN: 2114

Alfa AF: 0.129 Hom.: 354

Bravo AF: 0.0972

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.72
PhyloP100		0.38
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: rs3008621; hg19: chr1-222804046; COSMIC: COSV60517363;