1-117623034-C-T

Variant names:

• chr1-117623034-C-T
• rs756798728
• NM_017709.4:c.166C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_017709.4(TENT5C):​c.166C>T​(p.Arg56Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: TENT5C NM_017709.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.03
• Publications: 0 publications found

Genes affected

TENT5C (HGNC:24712): (terminal nucleotidyltransferase 5C) Enables RNA adenylyltransferase activity. Involved in mRNA stabilization. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017709.4. 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
	TENT5C	NM_017709.4	MANE Select	c.166C>T	p.Arg56Cys	missense	Exon 2 of 2	NP_060179.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TENT5C	ENST00000369448.4	TSL:1 MANE Select	c.166C>T	p.Arg56Cys	missense	Exon 2 of 2	ENSP00000358458.3	Q5VWP2
	TENT5C	ENST00000880490.1		c.166C>T	p.Arg56Cys	missense	Exon 3 of 3	ENSP00000550549.1
	TENT5C	ENST00000880491.1		c.166C>T	p.Arg56Cys	missense	Exon 2 of 2	ENSP00000550550.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251454 AF XY: 0.0000294

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461874 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 727238

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

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1111996

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152338 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74484

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.0000653 AC: 1 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.96	T
PhyloP100		6.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.83		Loss of disorder (P = 0.05)
MVP		0.46
MPC		1.8
ClinPred		0.78	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.80
Mutation Taster		=37/63	disease causing

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: rs756798728; hg19: chr1-118165656;