chr3-52230891-T-C

Position:

• chr3-52230891-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_007284.4(TWF2):​c.588A>G​(p.Lys196Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,609,484 control chromosomes in the GnomAD database, including 34,934 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4613 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30321 hom.)
• Consequence: TWF2 NM_007284.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=0.557 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TWF2	NM_007284.4	c.588A>G	p.Lys196Lys	synonymous_variant	6/9	ENST00000305533.10	NP_009215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWF2	ENST00000305533.10	c.588A>G	p.Lys196Lys	synonymous_variant	6/9	1	NM_007284.4	ENSP00000303908.4
ENSG00000173366	ENST00000494383.1	c.168A>G	p.Lys56Lys	synonymous_variant	2/5	2		ENSP00000417517.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34474 AN: 151444 Hom.: 4603 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0396

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.239

GnomAD3 exomes AF: 0.166 AC: 39993 AN: 241420 Hom.: 3941 AF XY: 0.162 AC XY: 21226 AN XY: 130642

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.0326

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.0971

Gnomad NFE exome AF: 0.194

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.197 AC: 286807 AN: 1457922 Hom.: 30321 Cov.: 34 AF XY: 0.194 AC XY: 140689 AN XY: 724910

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0284

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.228 AC: 34529 AN: 151562 Hom.: 4613 Cov.: 32 AF XY: 0.219 AC XY: 16208 AN XY: 74048

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0391

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.0924

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.240

Alfa AF: 0.207 Hom.: 5517

Bravo AF: 0.241

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	3.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs352143; hg19: chr3-52264907; COSMIC: COSV59726419; COSMIC: COSV59726419;