Variant 3-112013467-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001008272.2(TAGLN3):c.516C>G(p.Asn172Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TAGLN3
NM_001008272.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0920

Variant links:

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]

TAGLN3 links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein
TAGLN3	NM_001008272.2 linkuse as main transcript	c.516C>G	p.Asn172Lys	missense_variant	5/5	ENST00000478951.6	NP_001008273.1
TAGLN3	NM_001008273.2 linkuse as main transcript	c.516C>G	p.Asn172Lys	missense_variant	4/4		NP_001008274.1
TAGLN3	NM_013259.3 linkuse as main transcript	c.516C>G	p.Asn172Lys	missense_variant	5/5		NP_037391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAGLN3	ENST00000478951.6 linkuse as main transcript	c.516C>G	p.Asn172Lys	missense_variant	5/5	1	NM_001008272.2	ENSP00000419105	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251128

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS 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:

0.00000205

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.516C>G (p.N172K) alteration is located in exon 5 (coding exon 4) of the TAGLN3 gene. This alteration results from a C to G substitution at nucleotide position 516, causing the asparagine (N) at amino acid position 172 to be replaced by a lysine (K). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;T;T;.

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.93

.;D;.;.;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.32

T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.8

L;L;L;L;.

MutationTaster

Benign

0.94

D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Benign

0.12

Sift

Benign

0.16

T;T;T;T;T

Sift4G

Benign

0.40

T;T;T;T;T

Polyphen

0.075

B;B;B;B;.

Vest4

0.57

MutPred

0.36

Gain of ubiquitination at N172 (P = 0.0069);Gain of ubiquitination at N172 (P = 0.0069);Gain of ubiquitination at N172 (P = 0.0069);Gain of ubiquitination at N172 (P = 0.0069);.;

MVP

0.20

MPC

1.5

ClinPred

0.79

GERP RS

-0.66

Varity_R

0.22

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.22

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over