3-52229669-C-G

Variant names:

• chr3-52229669-C-G
• NM_007284.4:c.874G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_007284.4(TWF2):​c.874G>C​(p.Ala292Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,002 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A292S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TWF2 NM_007284.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102

Genes affected

TWF2 (HGNC:9621): (twinfilin actin binding protein 2) The protein encoded by this gene was identified by its interaction with the catalytic domain of protein kinase C-zeta. The encoded protein contains an actin-binding site and an ATP-binding site. It is most closely related to twinfilin (PTK9), a conserved actin monomer-binding protein. [provided by RefSeq, Jul 2008]

ENSG00000173366 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TWF2	NM_007284.4	c.874G>C	p.Ala292Pro	missense_variant	Exon 8 of 9	ENST00000305533.10	NP_009215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TWF2	ENST00000305533.10	c.874G>C	p.Ala292Pro	missense_variant	Exon 8 of 9	1	NM_007284.4	ENSP00000303908.4
ENSG00000173366	ENST00000494383.1	c.454G>C	p.Ala152Pro	missense_variant	Exon 4 of 5	2		ENSP00000417517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461002 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 726742

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: 0.0000696

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.062	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.17
Sift	Benign	0.14	T
Sift4G	Benign	0.31	T
Polyphen		0.47	P
Vest4		0.63
MutPred		0.38		Loss of stability (P = 0.0695);
MVP		0.33
MPC		0.64
ClinPred		0.68	D
GERP RS		-8.7
Varity_R		0.52
gMVP		0.71

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: chr3-52263685;