3-112013516-A-G

Variant names:

• chr3-112013516-A-G
• NM_001008272.2:c.565A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001008272.2(TAGLN3):​c.565A>G​(p.Met189Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TAGLN3 NM_001008272.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.94

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAGLN3	NM_001008272.2	c.565A>G	p.Met189Val	missense_variant	Exon 5 of 5	ENST00000478951.6	NP_001008273.1
TAGLN3	NM_001008273.2	c.565A>G	p.Met189Val	missense_variant	Exon 4 of 4		NP_001008274.1
TAGLN3	NM_013259.3	c.565A>G	p.Met189Val	missense_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.565A>G	p.Met189Val	missense_variant	Exon 5 of 5	1	NM_001008272.2	ENSP00000419105.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727228

Gnomad4 AFR exome AF: 0.00

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.565A>G (p.M189V) alteration is located in exon 5 (coding exon 4) of the TAGLN3 gene. This alteration results from a A to G substitution at nucleotide position 565, causing the methionine (M) at amino acid position 189 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.20	T
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	-0.28	T
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.032	D
MutPred		0.14		Gain of MoRF binding (P = 0.0287);
MVP		0.57
ClinPred		0.98	D
GERP RS		5.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-111732363;