Genetic Variant NM_001128596.3:c.967G>A (chr14-91792447-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate

The NM_001128596.3(TC2N):c.967G>A(p.Glu323Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,150 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 1 hom. )

Consequence

TC2N
NM_001128596.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.19

Publications

0 publications found

Variant links:

Genes affected

TC2N (HGNC:19859): (tandem C2 domains, nuclear) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TC2N links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29056978).

BP6

Variant 14-91792447-C-T is Benign according to our data. Variant chr14-91792447-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3453961.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128596.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TC2N	NM_001128596.3	MANE Select	c.967G>A	p.Glu323Lys	missense	Exon 9 of 12	NP_001122068.2	Q8N9U0-1
TC2N	NM_001128595.3		c.967G>A	p.Glu323Lys	missense	Exon 9 of 12	NP_001122067.2	Q8N9U0-1
TC2N	NM_152332.6		c.967G>A	p.Glu323Lys	missense	Exon 9 of 12	NP_689545.2	Q8N9U0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TC2N	ENST00000435962.7	TSL:2 MANE Select	c.967G>A	p.Glu323Lys	missense	Exon 9 of 12	ENSP00000387882.2	Q8N9U0-1
TC2N	ENST00000340892.9	TSL:1	c.967G>A	p.Glu323Lys	missense	Exon 9 of 12	ENSP00000343199.5	Q8N9U0-1
TC2N	ENST00000360594.9	TSL:1	c.967G>A	p.Glu323Lys	missense	Exon 9 of 12	ENSP00000353802.5	Q8N9U0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459150

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33436

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.0000349

AC:

AN:

85844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53266

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110222

Other (OTH)

AF:

0.00

AC:

AN:

60226

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.054

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.4

PhyloP100

2.2

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.22

Sift

Benign

0.041

Sift4G

Uncertain

0.019

Polyphen

0.013

Vest4

0.37

MutPred

0.57

Gain of MoRF binding (P = 0.0018)

MVP

0.66

MPC

0.074

ClinPred

0.96

GERP RS

2.8

Varity_R

0.23

gMVP

0.70

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over