rs10495197

chr1-222620358-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIA3	NM_198551.4	c.134-801C>T		intron_variant		ENST00000344922.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIA3	ENST00000344922.10	c.134-801C>T		intron_variant		5	NM_198551.4	P1
MIA3	ENST00000470521.1	n.146-801C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.0408

Gnomad4 FIN AF: 0.0439

Gnomad4 NFE AF: 0.0864

Gnomad4 OTH AF: 0.114

Alfa AF: 0.125 Hom.: 229

Bravo AF: 0.153

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.1
Dann	Benign	0.77

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

Publications

LitVar

Other links and lift over

dbSNP: rs10495197; hg19: chr1-222793700;