6-143060932-C-T

Position:

• chr6-143060932-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016108.4(AIG1):​c.7C>T​(p.Leu3Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AIG1 NM_016108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49

Genes affected

AIG1 (HGNC:21607): (androgen induced 1) Enables hydrolase activity. Involved in long-chain fatty acid catabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

AIG1 (HGNC:):

ACMG classification

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=0.24870569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIG1	NM_016108.4	c.7C>T	p.Leu3Phe	missense_variant	1/6	ENST00000357847.9	NP_057192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIG1	ENST00000357847.9	c.7C>T	p.Leu3Phe	missense_variant	1/6	1	NM_016108.4	ENSP00000350509.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457636 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725276

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.7C>T (p.L3F) alteration is located in exon 1 (coding exon 1) of the AIG1 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the leucine (L) at amino acid position 3 to be replaced by a phenylalanine (F). 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	Uncertain	0.38
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;.;.;.;T;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.25	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;.;N;N;.;N;N
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.1	N;.;N;.;D;.;N
REVEL	Benign	0.088
Sift	Pathogenic	0.0	D;.;D;.;D;.;D
Sift4G	Pathogenic	0.0	D;.;D;D;D;D;D
Polyphen		0.67, 0.83	.;.;P;.;.;P;.
Vest4		0.62, 0.62, 0.61, 0.51
MutPred		0.31		Loss of disorder (P = 0.119);Loss of disorder (P = 0.119);Loss of disorder (P = 0.119);Loss of disorder (P = 0.119);Loss of disorder (P = 0.119);Loss of disorder (P = 0.119);Loss of disorder (P = 0.119);
MVP		0.37
MPC		0.68
ClinPred		0.77	D
GERP RS		1.1
Varity_R		0.52
gMVP		0.18

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: rs374344989; hg19: chr6-143382069;