14-104701378-G-A

Position:

• chr14-104701378-G-A

Variant summary

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

The NM_022489.4(INF2):​c.13G>A​(p.Glu5Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,432,572 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E5V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: INF2 NM_022489.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3124694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INF2	NM_022489.4	c.13G>A	p.Glu5Lys	missense_variant	2/23	ENST00000392634.9
INF2	NM_001031714.4	c.13G>A	p.Glu5Lys	missense_variant	2/22
INF2	NM_032714.3	c.13G>A	p.Glu5Lys	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INF2	ENST00000392634.9	c.13G>A	p.Glu5Lys	missense_variant	2/23	5	NM_022489.4	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432572 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 709820

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: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Focal segmental glomerulosclerosis 5 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

MVZ Medizinische Genetik Mainz

Aug 09, 2024

ACMG Criteria: PM2_SUP,PP2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.091	.;.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.6	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0090	D;T;D
Sift4G	Uncertain	0.012	D;T;D
Polyphen		0.99	D;.;D
Vest4		0.33
MutPred		0.34		Gain of glycosylation at K5 (P = 0.0377);Gain of glycosylation at K5 (P = 0.0377);Gain of glycosylation at K5 (P = 0.0377);
MVP		0.68
MPC		2.5
ClinPred		0.88	D
GERP RS		4.3
Varity_R		0.20
gMVP		0.80

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: chr14-105167715;