chr3-112013467-C-T

Variant names:

• chr3-112013467-C-T
• rs759725437
• NM_001008272.2:c.516C>T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001008272.2(TAGLN3):​c.516C>T​(p.Asn172Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAGLN3 NM_001008272.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

Genes affected

TAGLN3 (HGNC:29868): (transgelin 3) Predicted to be involved in central nervous system development. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be active in cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08715826).
• BP7: Synonymous conserved (PhyloP=0.092 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGLN3	NM_001008272.2	c.516C>T	p.Asn172Asn	synonymous_variant	Exon 5 of 5	ENST00000478951.6	NP_001008273.1
TAGLN3	NM_001008273.2	c.516C>T	p.Asn172Asn	synonymous_variant	Exon 4 of 4		NP_001008274.1
TAGLN3	NM_013259.3	c.516C>T	p.Asn172Asn	synonymous_variant	Exon 5 of 5		NP_037391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAGLN3	ENST00000478951.6	c.516C>T	p.Asn172Asn	synonymous_variant	Exon 5 of 5	1	NM_001008272.2	ENSP00000419105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251128 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135722

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	8.9
DANN	Benign	0.88
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.77	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.080
Sift	Benign	0.12	T
Sift4G	Uncertain	0.0070	D
MutPred		0.27		Loss of solvent accessibility (P = 0.002);
MVP		0.082
ClinPred		0.11	T
GERP RS		-0.66

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

LitVar

Other links and lift over

dbSNP: rs759725437; hg19: chr3-111732314; COSMIC: COSV56328546;