14-91802295-C-G

Variant names:

• chr14-91802295-C-G
• rs779174077
• NM_001128596.3:c.428G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001128596.3(TC2N):​c.428G>C​(p.Arg143Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,449,792 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R143C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TC2N NM_001128596.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.15
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TC2N	NM_001128596.3	MANE Select	c.428G>C	p.Arg143Pro	missense	Exon 4 of 12	NP_001122068.2	Q8N9U0-1
	TC2N	NM_001128595.3		c.428G>C	p.Arg143Pro	missense	Exon 4 of 12	NP_001122067.2	Q8N9U0-1
	TC2N	NM_152332.6		c.428G>C	p.Arg143Pro	missense	Exon 4 of 12	NP_689545.2	Q8N9U0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TC2N	ENST00000435962.7	TSL:2 MANE Select	c.428G>C	p.Arg143Pro	missense	Exon 4 of 12	ENSP00000387882.2	Q8N9U0-1
	TC2N	ENST00000340892.9	TSL:1	c.428G>C	p.Arg143Pro	missense	Exon 4 of 12	ENSP00000343199.5	Q8N9U0-1
	TC2N	ENST00000360594.9	TSL:1	c.428G>C	p.Arg143Pro	missense	Exon 4 of 12	ENSP00000353802.5	Q8N9U0-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000125 AC: 3 AN: 239138 AF XY: 0.00000773

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1449792 Hom.: 0 Cov.: 34 AF XY: 0.00000971 AC XY: 7 AN XY: 720846

African (AFR) AF: 0.00 AC: 0 AN: 32670

American (AMR) AF: 0.00 AC: 0 AN: 42268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25988

East Asian (EAS) AF: 0.00 AC: 0 AN: 38630

South Asian (SAS) AF: 0.00 AC: 0 AN: 83500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1107708

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.2
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.11	T
Polyphen		0.96	P
Vest4		0.59
MutPred		0.61		Loss of stability (P = 0.0417)
MVP		0.46
MPC		0.33
ClinPred		0.89	D
GERP RS		4.7
Varity_R		0.39
gMVP		0.56
Mutation Taster		=50/50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs779174077; hg19: chr14-92268639;