rs10495197

Variant names:

• chr1-222620358-C-T
• rs10495197
• NM_198551.4:c.134-801C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198551.4(MIA3):​c.134-801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,192 control chromosomes in the GnomAD database, including 2,569 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 0.14 (2569 hom., cov: 34)
• Consequence: MIA3 NM_198551.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.702
• Publications: 2 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 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.134-801C>T		intron	N/A	NP_940953.2
	MIA3	NM_001324062.2		c.134-801C>T		intron	N/A	NP_001310991.1
	MIA3	NM_001324063.2		c.134-801C>T		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.134-801C>T		intron	N/A	ENSP00000340900.5	Q5JRA6-1
	MIA3	ENST00000883516.1		c.134-801C>T		intron	N/A	ENSP00000553575.1
	MIA3	ENST00000929361.1		c.134-801C>T		intron	N/A	ENSP00000599420.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21735 AN: 152074 Hom.: 2557 Cov.: 34

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.00538

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.143 AC: 21772 AN: 152192 Hom.: 2569 Cov.: 34 AF XY: 0.137 AC XY: 10220 AN XY: 74424

African (AFR) AF: 0.327 AC: 13582 AN: 41482

American (AMR) AF: 0.0796 AC: 1217 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5190

South Asian (SAS) AF: 0.0408 AC: 197 AN: 4824

European-Finnish (FIN) AF: 0.0439 AC: 465 AN: 10598

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0864 AC: 5878 AN: 68020

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.102 Hom.: 1529

Bravo AF: 0.153

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		-0.70
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10495197;

hg19: chr1-222793700;