3-112011775-C-T

Variant names:

• chr3-112011775-C-T
• rs1391136220
• NM_001008272.2:c.368C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001008272.2(TAGLN3):​c.368C>T​(p.Ala123Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,652 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A123E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAGLN3 NM_001008272.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.72
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3200786).

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.368C>T	p.Ala123Val	missense	Exon 4 of 5	NP_001008273.1	Q9UI15
	TAGLN3	NM_001008273.2		c.368C>T	p.Ala123Val	missense	Exon 3 of 4	NP_001008274.1	Q9UI15
	TAGLN3	NM_013259.3		c.368C>T	p.Ala123Val	missense	Exon 4 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.368C>T	p.Ala123Val	missense	Exon 4 of 5	ENSP00000419105.1	Q9UI15
	TAGLN3	ENST00000273368.8	TSL:1	c.368C>T	p.Ala123Val	missense	Exon 4 of 5	ENSP00000273368.4	Q9UI15
	TAGLN3	ENST00000455401.6	TSL:1	c.368C>T	p.Ala123Val	missense	Exon 3 of 4	ENSP00000391160.2	Q9UI15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249042 AF XY: 0.00000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000293

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459652 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726184

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.0000224 AC: 1 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.00 AC: 0 AN: 85944

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110864

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.22
Sift	Benign	0.076	T
Sift4G	Benign	0.20	T
Polyphen		0.84	P
Vest4		0.45
MutPred		0.47		Loss of glycosylation at K120 (P = 0.1797)
MVP		0.25
MPC		1.6
ClinPred		0.79	D
GERP RS		6.0
Varity_R		0.33
gMVP		0.79
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1391136220; hg19: chr3-111730622;