NM_205767.3:c.288G>C

Variant names:

• chr19-5678620-C-G
• rs775228688
• NM_205767.3:c.288G>C

Variant summary

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

The NM_205767.3(MICOS13):​c.288G>C​(p.Ser96Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S96S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MICOS13 NM_205767.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.83
• Publications: 0 publications found

Genes affected

MICOS13 (HGNC:33702): (mitochondrial contact site and cristae organizing system subunit 13) Involved in cristae formation. Located in mitochondrial crista junction and nucleoplasm. Part of MICOS complex. Implicated in combined oxidative phosphorylation deficiency 37. [provided by Alliance of Genome Resources, Apr 2022]

RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

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=-0.75).
• BP7: Synonymous conserved (PhyloP=-4.82 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_205767.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICOS13	NM_205767.3	MANE Select	c.288G>C	p.Ser96Ser	synonymous	Exon 4 of 4	NP_991330.1	Q5XKP0
	MICOS13	NM_001308240.2		c.354G>C	p.Ser118Ser	synonymous	Exon 5 of 5	NP_001295169.1	A0A140TA86
	MICOS13	NM_001365761.2		c.354G>C	p.Ser118Ser	synonymous	Exon 4 of 4	NP_001352690.1	A0A140TA86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICOS13	ENST00000309324.9	TSL:1 MANE Select	c.288G>C	p.Ser96Ser	synonymous	Exon 4 of 4	ENSP00000309561.3	Q5XKP0
	MICOS13	ENST00000587950.5	TSL:2	c.354G>C	p.Ser118Ser	synonymous	Exon 4 of 4	ENSP00000468723.1	A0A140TA86
	MICOS13	ENST00000896351.1		c.315G>C	p.Ser105Ser	synonymous	Exon 4 of 4	ENSP00000566410.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.14
DANN	Benign	0.77
PhyloP100		-4.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs775228688; hg19: chr19-5678631;