NM_001008272.2:c.516C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008272.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAGLN3	NM_001008272.2	MANE Select	c.516C>T	p.Asn172Asn	synonymous	Exon 5 of 5	NP_001008273.1	Q9UI15
	TAGLN3	NM_001008273.2		c.516C>T	p.Asn172Asn	synonymous	Exon 4 of 4	NP_001008274.1	Q9UI15
	TAGLN3	NM_013259.3		c.516C>T	p.Asn172Asn	synonymous	Exon 5 of 5	NP_037391.2	Q9UI15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAGLN3	ENST00000478951.6	TSL:1 MANE Select	c.516C>T	p.Asn172Asn	synonymous	Exon 5 of 5	ENSP00000419105.1	Q9UI15
	TAGLN3	ENST00000273368.8	TSL:1	c.516C>T	p.Asn172Asn	synonymous	Exon 5 of 5	ENSP00000273368.4	Q9UI15
	TAGLN3	ENST00000455401.6	TSL:1	c.516C>T	p.Asn172Asn	synonymous	Exon 4 of 4	ENSP00000391160.2	Q9UI15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251128 AF XY: 0.00

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 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

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
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
PhyloP100		0.092
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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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