rs3757251

Positions:

• chr6-13790904-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001031713.4(MCUR1):​c.1025-40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,446,734 control chromosomes in the GnomAD database, including 1,949 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 0.061 (461 hom., cov: 31)
  • Exomes 𝑓: 0.043 (1488 hom.)
• Consequence: MCUR1 NM_001031713.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

MCUR1 (HGNC:21097): (mitochondrial calcium uniporter regulator 1) Involved in calcium import into the mitochondrion and positive regulation of mitochondrial calcium ion concentration. Is integral component of mitochondrial inner 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCUR1	NM_001031713.4	c.1025-40A>G		intron_variant		ENST00000379170.9	NP_001026883.1
MCUR1	XM_011514802.2	c.1024+974A>G		intron_variant			XP_011513104.1
MCUR1	XM_047419249.1	c.1268-40A>G		intron_variant			XP_047275205.1
MCUR1	XR_007059329.1	n.1243+974A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUR1	ENST00000379170.9	c.1025-40A>G		intron_variant		1	NM_001031713.4	ENSP00000368468	P1
MCUR1	ENST00000607303.1	c.341+974A>G		intron_variant		3		ENSP00000476106
MCUR1	ENST00000488770.1	c.*837-40A>G		intron_variant, NMD_transcript_variant		2		ENSP00000476162

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9314 AN: 152138 Hom.: 459 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0366

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.0613

Gnomad FIN AF: 0.00707

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0512

GnomAD3 exomes AF: 0.0417 AC: 9103 AN: 218314 Hom.: 296 AF XY: 0.0415 AC XY: 4918 AN XY: 118588

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.0286

Gnomad ASJ exome AF: 0.0362

Gnomad EAS exome AF: 0.0192

Gnomad SAS exome AF: 0.0575

Gnomad FIN exome AF: 0.00833

Gnomad NFE exome AF: 0.0394

Gnomad OTH exome AF: 0.0355

GnomAD4 exome AF: 0.0430 AC: 55600 AN: 1294478 Hom.: 1488 Cov.: 17 AF XY: 0.0431 AC XY: 28055 AN XY: 651228

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.0289

Gnomad4 ASJ exome AF: 0.0327

Gnomad4 EAS exome AF: 0.0230

Gnomad4 SAS exome AF: 0.0532

Gnomad4 FIN exome AF: 0.00787

Gnomad4 NFE exome AF: 0.0427

Gnomad4 OTH exome AF: 0.0477

GnomAD4 genome AF: 0.0613 AC: 9334 AN: 152256 Hom.: 461 Cov.: 31 AF XY: 0.0593 AC XY: 4415 AN XY: 74452

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0366

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.00707

Gnomad4 NFE AF: 0.0390

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0509 Hom.: 64

Bravo AF: 0.0642

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3757251; hg19: chr6-13791136;