rs17011666

Positions:

• chr1-222625623-G-A
• chr1-222625623-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIA3	NM_198551.4	c.354+769G>A		intron_variant		ENST00000344922.10	NP_940953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIA3	ENST00000344922.10	c.354+769G>A		intron_variant		5	NM_198551.4	ENSP00000340900	P1
MIA3	ENST00000470521.1	n.366+769G>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.584

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.797

Gnomad4 OTH AF: 0.694

Alfa AF: 0.768 Hom.: 47930

Bravo AF: 0.706

Asia WGS AF: 0.555 AC: 1934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.80

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: rs17011666; hg19: chr1-222798965; COSMIC: COSV60511260; COSMIC: COSV60511260;