rs9832803

Variant names:

• chr3-158673335-C-G
• rs9832803
• NM_024996.7:c.1601+6949C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-158673335-C-G
• chr3-158673335-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024996.7(GFM1):​c.1601+6949C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 151,740 control chromosomes in the GnomAD database, including 14,265 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 0.42 (14265 hom., cov: 31)
• Consequence: GFM1 NM_024996.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42
• Publications: 10 publications found

Genes affected

GFM1 (HGNC:13780): (G elongation factor mitochondrial 1) Eukaryotes contain two protein translational systems, one in the cytoplasm and one in the mitochondria. Mitochondrial translation is crucial for maintaining mitochondrial function and mutations in this system lead to a breakdown in the respiratory chain-oxidative phosphorylation system and to impaired maintenance of mitochondrial DNA. This gene encodes one of the mitochondrial translation elongation factors. Its role in the regulation of normal mitochondrial function and in different disease states attributed to mitochondrial dysfunction is not known. [provided by RefSeq, Jul 2008]

GFM1 Gene-Disease associations (from GenCC):

• hepatoencephalopathy due to combined oxidative phosphorylation defect type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024996.7. 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
	GFM1	NM_024996.7	MANE Select	c.1601+6949C>G		intron	N/A	NP_079272.4
	GFM1	NM_001308164.2		c.1658+6949C>G		intron	N/A	NP_001295093.1	Q96RP9-2
	GFM1	NM_001374355.1		c.1520+6949C>G		intron	N/A	NP_001361284.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFM1	ENST00000486715.6	TSL:1 MANE Select	c.1601+6949C>G		intron	N/A	ENSP00000419038.1	Q96RP9-1
	GFM1	ENST00000867690.1		c.1679+6949C>G		intron	N/A	ENSP00000537749.1
	GFM1	ENST00000867689.1		c.1673+6949C>G		intron	N/A	ENSP00000537748.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63013 AN: 151622 Hom.: 14238 Cov.: 31

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.416 AC: 63094 AN: 151740 Hom.: 14265 Cov.: 31 AF XY: 0.411 AC XY: 30472 AN XY: 74158

African (AFR) AF: 0.601 AC: 24858 AN: 41360

American (AMR) AF: 0.343 AC: 5224 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3470

East Asian (EAS) AF: 0.157 AC: 812 AN: 5160

South Asian (SAS) AF: 0.377 AC: 1811 AN: 4810

European-Finnish (FIN) AF: 0.308 AC: 3234 AN: 10492

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24560 AN: 67900

Other (OTH) AF: 0.408 AC: 857 AN: 2102

Alfa AF: 0.213 Hom.: 436

Bravo AF: 0.427

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.12
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs9832803; hg19: chr3-158391124;