14-104714295-C-G

Variant names:

• chr14-104714295-C-G
• NM_022489.4:c.3133C>G

Variant summary

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

The NM_022489.4(INF2):​c.3133C>G​(p.Arg1045Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: INF2 NM_022489.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430

Genes affected

INF2 (HGNC:23791): (inverted formin 2) This gene represents a member of the formin family of proteins. It is considered a diaphanous formin due to the presence of a diaphanous inhibitory domain located at the N-terminus of the encoded protein. Studies of a similar mouse protein indicate that the protein encoded by this locus may function in polymerization and depolymerization of actin filaments. Mutations at this locus have been associated with focal segmental glomerulosclerosis 5.[provided by RefSeq, Aug 2010]

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=0.09064475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INF2	NM_022489.4	c.3133C>G	p.Arg1045Gly	missense_variant	Exon 21 of 23	ENST00000392634.9	NP_071934.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INF2	ENST00000392634.9	c.3133C>G	p.Arg1045Gly	missense_variant	Exon 21 of 23	5	NM_022489.4	ENSP00000376410.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439836 Hom.: 0 Cov.: 70 AF XY: 0.00 AC XY: 0 AN XY: 714582

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: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.046	.;T;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.6	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.040	D;D;.
Sift4G	Benign	0.45	T;T;T
Polyphen		0.26	B;B;.
Vest4		0.17
MutPred		0.32		Gain of catalytic residue at R1045 (P = 0.01);Gain of catalytic residue at R1045 (P = 0.01);.;
MVP		0.17
MPC		0.32
ClinPred		0.15	T
GERP RS		1.8
Varity_R		0.12
gMVP		0.097

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-105180632;