9-131106192-G-A

Variant names:

• chr9-131106192-G-A
• rs1830742766
• NM_031426.4:c.94-5405G>A

Variant summary

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

The NM_001185095.2(AIF1L):​c.98G>A​(p.Cys33Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: AIF1L NM_001185095.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.307

Genes affected

AIF1L (HGNC:28904): (allograft inflammatory factor 1 like) Enables actin filament binding activity. Predicted to be involved in actin filament bundle assembly and ruffle assembly. Located in actin cytoskeleton and focal adhesion. Colocalizes with actin filament. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

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=0.080768704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIF1L	NM_031426.4	c.94-5405G>A		intron_variant	Intron 2 of 5	ENST00000247291.8	NP_113614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIF1L	ENST00000247291.8	c.94-5405G>A		intron_variant	Intron 2 of 5	1	NM_031426.4	ENSP00000247291.3
AIF1L	ENST00000372302.5	c.94-5405G>A		intron_variant	Intron 2 of 5	2		ENSP00000361376.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383224 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 682558

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98G>A (p.C33Y) alteration is located in exon 3 (coding exon 3) of the AIF1L gene. This alteration results from a G to A substitution at nucleotide position 98, causing the cysteine (C) at amino acid position 33 to be replaced by a tyrosine (Y). 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
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.8
DANN	Benign	0.67
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.039
Sift	Benign	0.059	T
Sift4G	Uncertain	0.029	D
Polyphen		0.51	P
Vest4		0.15
MutPred		0.41		Gain of loop (P = 3e-04);
MVP		0.32
MPC		0.45
ClinPred		0.075	T
GERP RS		0.62
gMVP		0.49

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: rs1830742766; hg19: chr9-133981579;