rs1729166878

Variant names:

• chr4-109659025-G-A
• rs1729166878
• NM_017918.5:c.114G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-109659025-G-A
• chr4-109659025-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017918.5(MCUB):​c.114G>A​(p.Lys38Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: MCUB NM_017918.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 0 publications found

Genes affected

MCUB (HGNC:26076): (mitochondrial calcium uniporter dominant negative subunit beta) Predicted to enable calcium channel inhibitor activity. Predicted to be involved in calcium import into the mitochondrion and mitochondrial calcium ion homeostasis. Located in mitochondrion and nucleoplasm. Is integral component of mitochondrial inner membrane. Part of uniplex complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=0.316 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCUB	NM_017918.5	c.114G>A	p.Lys38Lys	synonymous_variant	Exon 2 of 8	ENST00000394650.7	NP_060388.2
MCUB	XM_006714246.4	c.27G>A	p.Lys9Lys	synonymous_variant	Exon 2 of 8		XP_006714309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCUB	ENST00000394650.7	c.114G>A	p.Lys38Lys	synonymous_variant	Exon 2 of 8	1	NM_017918.5	ENSP00000378145.4
MCUB	ENST00000472310.5	n.243G>A		non_coding_transcript_exon_variant	Exon 2 of 5	1
MCUB	ENST00000452915.3	n.209G>A		non_coding_transcript_exon_variant	Exon 3 of 6	5
MCUB	ENST00000515114.3	n.240G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386674 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 684812

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31330

American (AMR) AF: 0.00 AC: 0 AN: 35682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25114

East Asian (EAS) AF: 0.00 AC: 0 AN: 35820

South Asian (SAS) AF: 0.00 AC: 0 AN: 78888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067440

Other (OTH) AF: 0.00 AC: 0 AN: 57516

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		0.32

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

Other links and lift over

dbSNP: rs1729166878; hg19: chr4-110580181;