3-158645968-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024996.7(GFM1):c.234+187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00681 in 824,270 control chromosomes in the GnomAD database, including 226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (153 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (73 hom.)
• Consequence: GFM1 NM_024996.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.614

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]

LXN (HGNC:13347): (latexin) This gene encodes the only known protein inhibitor of zinc-dependent metallocarboxypeptidases. The encoded protein, latexin, downregulates the population size of hematopoietic stem cells. This protein is found to be downregulated in cancer cells because of promoter hypermethylation. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 3-158645968-A-G is Benign according to our data. Variant chr3-158645968-A-G is described in ClinVar as [Benign]. Clinvar id is 1247283.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFM1	NM_024996.7	c.234+187A>G		intron_variant		ENST00000486715.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFM1	ENST00000486715.6	c.234+187A>G		intron_variant		1	NM_024996.7	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3672 AN: 152180 Hom.: 152 Cov.: 33

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.00288 AC: 1932 AN: 671972 Hom.: 73 Cov.: 9 AF XY: 0.00239 AC XY: 850 AN XY: 354976

Gnomad4 AFR exome AF: 0.0853

Gnomad4 AMR exome AF: 0.00438

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000168

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000332

Gnomad4 OTH exome AF: 0.00725

GnomAD4 genome AF: 0.0242 AC: 3680 AN: 152298 Hom.: 153 Cov.: 33 AF XY: 0.0233 AC XY: 1734 AN XY: 74466

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.00549

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0175 Hom.: 9

Bravo AF: 0.0270

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.6
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs78679143; hg19: chr3-158363757;