chr6-143284220-A-G

Position:

• chr6-143284220-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016108.4(AIG1):​c.510A>G​(p.Ile170Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AIG1 NM_016108.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31352678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIG1	NM_016108.4	c.510A>G	p.Ile170Met	missense_variant	4/6	ENST00000357847.9	NP_057192.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIG1	ENST00000357847.9	c.510A>G	p.Ile170Met	missense_variant	4/6	1	NM_016108.4	ENSP00000350509.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249822 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134932

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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

Aug 17, 2021

The c.510A>G (p.I170M) alteration is located in exon 4 (coding exon 4) of the AIG1 gene. This alteration results from a A to G substitution at nucleotide position 510, causing the isoleucine (I) at amino acid position 170 to be replaced by a methionine (M). 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	0.26
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.019	T;T;.;.;T;T
Eigen	Benign	-0.076
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.84	T;T;T;T;T;D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.31	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;.;.;M;M;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.0	N;N;.;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.059	T;T;.;T;T;T
Sift4G	Benign	0.27	T;T;.;T;T;T
Polyphen		0.23	.;.;.;B;.;.
Vest4		0.58, 0.58
MutPred		0.64		.;.;Loss of catalytic residue at I170 (P = 0.0728);Loss of catalytic residue at I170 (P = 0.0728);Loss of catalytic residue at I170 (P = 0.0728);.;
MVP		0.10
MPC		0.40
ClinPred		0.33	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs772388736; hg19: chr6-143605357;