3-112011775-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001008272.2(TAGLN3):​c.368C>A​(p.Ala123Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAGLN3 NM_001008272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.752

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>A	p.Ala123Glu	missense	Exon 4 of 5	NP_001008273.1	Q9UI15
	TAGLN3	NM_001008273.2		c.368C>A	p.Ala123Glu	missense	Exon 3 of 4	NP_001008274.1	Q9UI15
	TAGLN3	NM_013259.3		c.368C>A	p.Ala123Glu	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>A	p.Ala123Glu	missense	Exon 4 of 5	ENSP00000419105.1	Q9UI15
	TAGLN3	ENST00000273368.8	TSL:1	c.368C>A	p.Ala123Glu	missense	Exon 4 of 5	ENSP00000273368.4	Q9UI15
	TAGLN3	ENST00000455401.6	TSL:1	c.368C>A	p.Ala123Glu	missense	Exon 3 of 4	ENSP00000391160.2	Q9UI15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459650 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726182

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

American (AMR) AF: 0.00 AC: 0 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

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: 9.00e-7 AC: 1 AN: 1110864

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.74	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	0.0019	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.011	D
Sift4G	Benign	0.081	T
Polyphen		0.95	P
Vest4		0.80
MutPred		0.49		Gain of disorder (P = 0.0876)
MVP		0.49
MPC		2.0
ClinPred		0.97	D
GERP RS		6.0
Varity_R		0.64
gMVP		0.93
Mutation Taster		=63/37	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;