3-111999549-G-C

Variant names:

• chr3-111999549-G-C
• rs763508176
• NM_001008272.2:c.127G>C

Variant summary

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

The NM_001008272.2(TAGLN3):​c.127G>C​(p.Glu43Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. E43K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAGLN3 NM_001008272.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.76
• 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=0.40859792).

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.127G>C	p.Glu43Gln	missense	Exon 2 of 5	NP_001008273.1	Q9UI15
	TAGLN3	NM_001008273.2		c.127G>C	p.Glu43Gln	missense	Exon 1 of 4	NP_001008274.1	Q9UI15
	TAGLN3	NM_013259.3		c.127G>C	p.Glu43Gln	missense	Exon 2 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.127G>C	p.Glu43Gln	missense	Exon 2 of 5	ENSP00000419105.1	Q9UI15
	TAGLN3	ENST00000273368.8	TSL:1	c.127G>C	p.Glu43Gln	missense	Exon 2 of 5	ENSP00000273368.4	Q9UI15
	TAGLN3	ENST00000455401.6	TSL:1	c.127G>C	p.Glu43Gln	missense	Exon 1 of 4	ENSP00000391160.2	Q9UI15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	0.076
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	1.1	L
PhyloP100		7.8
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.29
Sift	Benign	0.063	T
Sift4G	Benign	0.56	T
Polyphen		0.11	B
Vest4		0.10
MutPred		0.55		Loss of glycosylation at P47 (P = 0.0472)
MVP		0.63
MPC		0.82
ClinPred		0.95	D
GERP RS		4.5
PromoterAI		0.013	Neutral
Varity_R		0.21
gMVP		0.62
Mutation Taster		=75/25	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: rs763508176; hg19: chr3-111718396;