1-222650187-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198551.4(MIA3):​c.3632-105A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIA3	NM_198551.4	c.3632-105A>T		intron_variant	Intron 8 of 27	ENST00000344922.10	NP_940953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIA3	ENST00000344922.10	c.3632-105A>T		intron_variant	Intron 8 of 27	5	NM_198551.4	ENSP00000340900.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 585420 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 314794

African (AFR) AF: 0.00 AC: 0 AN: 15884

American (AMR) AF: 0.00 AC: 0 AN: 33974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19694

East Asian (EAS) AF: 0.00 AC: 0 AN: 31404

South Asian (SAS) AF: 0.00 AC: 0 AN: 61904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4022

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 340732

Other (OTH) AF: 0.00 AC: 0 AN: 30920

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 150448

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055
DANN	Benign	0.074
PhyloP100		-0.63

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;