6-108324005-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145315.5(AFG1L):ā€‹c.320A>Gā€‹(p.Asp107Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

AFG1L
NM_145315.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1699144).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AFG1LNM_145315.5 linkuse as main transcriptc.320A>G p.Asp107Gly missense_variant 2/13 ENST00000368977.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AFG1LENST00000368977.9 linkuse as main transcriptc.320A>G p.Asp107Gly missense_variant 2/131 NM_145315.5 P1
AFG1LENST00000437715.1 linkuse as main transcriptc.221A>G p.Asp74Gly missense_variant 3/65
AFG1LENST00000421954.5 linkuse as main transcriptc.18+28787A>G intron_variant 5
AFG1LENST00000430458.1 linkuse as main transcriptn.409A>G non_coding_transcript_exon_variant 2/45

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461786
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 03, 2023The c.320A>G (p.D107G) alteration is located in exon 2 (coding exon 2) of the LACE1 gene. This alteration results from a A to G substitution at nucleotide position 320, causing the aspartic acid (D) at amino acid position 107 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.058
T;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.064
FATHMM_MKL
Benign
0.43
N
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.69
N
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.3
N;D
REVEL
Benign
0.10
Sift
Benign
0.15
T;T
Sift4G
Benign
0.27
T;T
Polyphen
0.0010
B;.
Vest4
0.28
MutPred
0.56
Loss of stability (P = 0.0124);.;
MVP
0.39
MPC
0.23
ClinPred
0.61
D
GERP RS
3.0
Varity_R
0.16
gMVP
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1777929147; hg19: chr6-108645209; API