6-13790904-T-C

Variant names:

• chr6-13790904-T-C
• rs3757251
• NM_001031713.4:c.1025-40A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000307512 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MCUR1	NM_001031713.4	c.1025-40A>G		intron_variant	Intron 8 of 8	ENST00000379170.9	NP_001026883.1
MCUR1	XM_047419249.1	c.1268-40A>G		intron_variant	Intron 8 of 8		XP_047275205.1
MCUR1	XM_011514802.2	c.1024+974A>G		intron_variant	Intron 8 of 8		XP_011513104.1
MCUR1	XR_007059329.1	n.1243+974A>G		intron_variant	Intron 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCUR1	ENST00000379170.9	c.1025-40A>G		intron_variant	Intron 8 of 8	1	NM_001031713.4	ENSP00000368468.3
MCUR1	ENST00000607303.1	c.340+974A>G		intron_variant	Intron 5 of 6	3		ENSP00000476106.1
MCUR1	ENST00000488770.1	n.*837-40A>G		intron_variant	Intron 9 of 9	2		ENSP00000476162.1
ENSG00000307512	ENST00000826661.1	n.369-151T>C		intron_variant	Intron 2 of 2

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

GnomAD2 exomes AF: 0.0417 AC: 9103 AN: 218314 AF XY: 0.0415

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 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

African (AFR) AF: 0.132 AC: 3733 AN: 28352

American (AMR) AF: 0.0289 AC: 1017 AN: 35240

Ashkenazi Jewish (ASJ) AF: 0.0327 AC: 771 AN: 23558

East Asian (EAS) AF: 0.0230 AC: 874 AN: 37970

South Asian (SAS) AF: 0.0532 AC: 4121 AN: 77414

European-Finnish (FIN) AF: 0.00787 AC: 414 AN: 52632

Middle Eastern (MID) AF: 0.0539 AC: 289 AN: 5366

European-Non Finnish (NFE) AF: 0.0427 AC: 41789 AN: 979586

Other (OTH) AF: 0.0477 AC: 2592 AN: 54360

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

African (AFR) AF: 0.130 AC: 5409 AN: 41544

American (AMR) AF: 0.0366 AC: 559 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.0181 AC: 94 AN: 5182

South Asian (SAS) AF: 0.0615 AC: 297 AN: 4826

European-Finnish (FIN) AF: 0.00707 AC: 75 AN: 10610

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0390 AC: 2650 AN: 68016

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0496 Hom.: 378

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
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3757251; hg19: chr6-13791136;