rs16929951

chr10-72506460-T-Cchr10-72506460-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001195518.2(MICU1):c.652+1695A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 152,350 control chromosomes in the GnomAD database, including 6 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 0.0029 (6 hom., cov: 32)
• Consequence: MICU1 NM_001195518.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

Genes affected

MICU1 (HGNC:1530): (mitochondrial calcium uptake 1) This gene encodes an essential regulator of mitochondrial Ca2+ uptake under basal conditions. The encoded protein interacts with the mitochondrial calcium uniporter, a mitochondrial inner membrane Ca2+ channel, and is essential in preventing mitochondrial Ca2+ overload, which can cause excessive production of reactive oxygen species and cell stress. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00292 (445/152350) while in subpopulation EAS AF= 0.0464 (241/5190). AF 95% confidence interval is 0.0416. There are 6 homozygotes in gnomad4. There are 259 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICU1	NM_001195518.2	c.652+1695A>G		intron_variant		ENST00000361114.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICU1	ENST00000361114.10	c.652+1695A>G		intron_variant		1	NM_001195518.2	P4

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 445 AN: 152232 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.00191

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

GnomAD4 genome AF: 0.00292 AC: 445 AN: 152350 Hom.: 6 Cov.: 32 AF XY: 0.00348 AC XY: 259 AN XY: 74510

Gnomad4 AFR AF: 0.000168

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0464

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00678

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00120 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.74

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: rs16929951; hg19: chr10-74266218;