1-222630704-G-A

Position:

• chr1-222630704-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	Protein	UniProt
MIA3	NM_198551.4	c.3169+315G>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.3169+315G>A		intron_variant		5	NM_198551.4	ENSP00000340900	P1
MIA3	ENST00000354906.7	c.1916+315G>A		intron_variant		5		ENSP00000355062
MIA3	ENST00000470521.1	n.3181+315G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.0927

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0996

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.125

Alfa AF: 0.120 Hom.: 191

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

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: rs3008621; hg19: chr1-222804046; COSMIC: COSV60517363;