chr3-52231199-G-A

Position:

• chr3-52231199-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_007284.4(TWF2):​c.411C>T​(p.His137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,614,020 control chromosomes in the GnomAD database, including 1,792 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 0.035 (138 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1654 hom.)
• Consequence: TWF2 NM_007284.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0351 (5336/152208) while in subpopulation NFE AF= 0.0492 (3345/67982). AF 95% confidence interval is 0.0478. There are 138 homozygotes in gnomad4. There are 2471 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5336 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TWF2	NM_007284.4	c.411C>T	p.His137=	synonymous_variant	5/9	ENST00000305533.10	NP_009215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TWF2	ENST00000305533.10	c.411C>T	p.His137=	synonymous_variant	5/9	1	NM_007284.4	ENSP00000303908	P1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5335 AN: 152090 Hom.: 136 Cov.: 33

Gnomad AFR AF: 0.00939

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0460

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0298

Gnomad SAS AF: 0.0224

Gnomad FIN AF: 0.0307

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0397

GnomAD3 exomes AF: 0.0369 AC: 9271 AN: 251404 Hom.: 224 AF XY: 0.0373 AC XY: 5065 AN XY: 135876

Gnomad AFR exome AF: 0.00818

Gnomad AMR exome AF: 0.0343

Gnomad ASJ exome AF: 0.0253

Gnomad EAS exome AF: 0.0260

Gnomad SAS exome AF: 0.0195

Gnomad FIN exome AF: 0.0331

Gnomad NFE exome AF: 0.0494

Gnomad OTH exome AF: 0.0463

GnomAD4 exome AF: 0.0445 AC: 65035 AN: 1461812 Hom.: 1654 Cov.: 33 AF XY: 0.0441 AC XY: 32106 AN XY: 727222

Gnomad4 AFR exome AF: 0.00815

Gnomad4 AMR exome AF: 0.0367

Gnomad4 ASJ exome AF: 0.0268

Gnomad4 EAS exome AF: 0.0209

Gnomad4 SAS exome AF: 0.0199

Gnomad4 FIN exome AF: 0.0339

Gnomad4 NFE exome AF: 0.0496

Gnomad4 OTH exome AF: 0.0448

GnomAD4 genome AF: 0.0351 AC: 5336 AN: 152208 Hom.: 138 Cov.: 33 AF XY: 0.0332 AC XY: 2471 AN XY: 74410

Gnomad4 AFR AF: 0.00934

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0307

Gnomad4 NFE AF: 0.0492

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0472 Hom.: 223

Bravo AF: 0.0357

Asia WGS AF: 0.0350 AC: 120 AN: 3478

EpiCase AF: 0.0496

EpiControl AF: 0.0539

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs164637; hg19: chr3-52265215;