NM_145315.5:c.807+16499T>G

Variant names:

• chr6-108418553-T-G
• rs9486880
• NM_145315.5:c.807+16499T>G

Variant summary

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

The NM_145315.5(AFG1L):​c.807+16499T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,002 control chromosomes in the GnomAD database, including 9,856 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 0.35 (9856 hom., cov: 31)
• Consequence: AFG1L NM_145315.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 2 publications found

Genes affected

AFG1L (HGNC:16411): (AFG1 like ATPase) This gene encodes a mitochondrial integral membrane protein that plays a role in mitochondrial protein homeostasis. The protein contains a P-loop motif and a five-domain structure that is conserved in fly, yeast, and bacteria. It functions to mediate the degradation of nuclear-encoded complex IV subunits. Two conserved estrogen receptor binding sites are located within 2.5 kb of this gene. Polymorphisms in this gene have been associated with bipolar disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2016]

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 (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145315.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFG1L	NM_145315.5	MANE Select	c.807+16499T>G		intron	N/A	NP_660358.2
	AFG1L	NM_001323005.2		c.807+16499T>G		intron	N/A	NP_001309934.1
	AFG1L	NR_136553.2		n.397-28661T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFG1L	ENST00000368977.9	TSL:1 MANE Select	c.807+16499T>G		intron	N/A	ENSP00000357973.3
	AFG1L	ENST00000421954.5	TSL:5	c.408+16499T>G		intron	N/A	ENSP00000398225.1
	AFG1L	ENST00000431865.1	TSL:5	n.230-28661T>G		intron	N/A	ENSP00000415484.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53514 AN: 151884 Hom.: 9858 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.352 AC: 53522 AN: 152002 Hom.: 9856 Cov.: 31 AF XY: 0.347 AC XY: 25768 AN XY: 74264

African (AFR) AF: 0.248 AC: 10292 AN: 41468

American (AMR) AF: 0.339 AC: 5176 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1088 AN: 5174

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4816

European-Finnish (FIN) AF: 0.392 AC: 4134 AN: 10554

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28837 AN: 67938

Other (OTH) AF: 0.383 AC: 808 AN: 2112

Alfa AF: 0.406 Hom.: 23206

Bravo AF: 0.346

Asia WGS AF: 0.244 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.8
DANN	Benign	0.53
PhyloP100		0.51
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: rs9486880; hg19: chr6-108739757;