9-131096861-C-T

Variant names:

• chr9-131096861-C-T
• rs774289256
• NM_031426.4:c.91C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031426.4(AIF1L):​c.91C>T​(p.Arg31Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000912 in 1,534,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: AIF1L NM_031426.4 missense, splice_region
• Scores: Splicing: ADA: 0.01892
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.223
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23422945).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1L	NM_031426.4	MANE Select	c.91C>T	p.Arg31Trp	missense splice_region	Exon 2 of 6	NP_113614.1	Q9BQI0-1
	AIF1L	NM_001185095.2		c.91C>T	p.Arg31Trp	missense splice_region	Exon 2 of 7	NP_001172024.1	Q9BQI0-2
	AIF1L	NM_001185096.2		c.91C>T	p.Arg31Trp	missense splice_region	Exon 2 of 6	NP_001172025.1	Q9BQI0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIF1L	ENST00000247291.8	TSL:1 MANE Select	c.91C>T	p.Arg31Trp	missense splice_region	Exon 2 of 6	ENSP00000247291.3	Q9BQI0-1
	AIF1L	ENST00000372302.5	TSL:2	c.91C>T	p.Arg31Trp	missense splice_region	Exon 2 of 6	ENSP00000361376.1	Q9BQI0-3
	AIF1L	ENST00000372300.5	TSL:1	c.91C>T	p.Arg31Trp	missense splice_region	Exon 2 of 6	ENSP00000361374.1	Q9BQI0-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000154 AC: 2 AN: 129646 AF XY: 0.0000285

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000540

GnomAD4 exome AF: 0.00000940 AC: 13 AN: 1382484 Hom.: 0 Cov.: 32 AF XY: 0.0000117 AC XY: 8 AN XY: 682216

African (AFR) AF: 0.000101 AC: 3 AN: 29672

American (AMR) AF: 0.00 AC: 0 AN: 33784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24682

East Asian (EAS) AF: 0.00 AC: 0 AN: 33608

South Asian (SAS) AF: 0.0000129 AC: 1 AN: 77692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46236

Middle Eastern (MID) AF: 0.000367 AC: 2 AN: 5450

European-Non Finnish (NFE) AF: 0.00000559 AC: 6 AN: 1073998

Other (OTH) AF: 0.0000174 AC: 1 AN: 57362

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152192 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000106 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	T
Eigen	Benign	0.015
Eigen_PC	Benign	-0.0090
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.22
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.13
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.44		Loss of disorder (P = 4e-04)
MVP		0.60
MPC		0.91
ClinPred		0.75	D
GERP RS		2.1
PromoterAI		-0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.52
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.019
dbscSNV1_RF	Benign	0.20
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

Other links and lift over

dbSNP: rs774289256; hg19: chr9-133972248;