1-26994303-C-T

Variant names:

• chr1-26994303-C-T
• rs1298194314
• NM_001013642.3:c.517C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001013642.3(TRNP1):​c.517C>T​(p.Pro173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000872 in 1,146,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: TRNP1 NM_001013642.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.131
• Publications: 0 publications found

Genes affected

TRNP1 (HGNC:34348): (TMF1 regulated nuclear protein 1) Predicted to enable DNA binding activity. Predicted to be involved in several processes, including cerebellar cortex morphogenesis; neural precursor cell proliferation; and regulation of cell population proliferation. Predicted to be active in nucleus. Predicted to colocalize with euchromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.015164971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013642.3. 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
	TRNP1	NM_001013642.3	MANE Select	c.517C>T	p.Pro173Ser	missense	Exon 1 of 2	NP_001013664.2	Q6NT89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNP1	ENST00000522111.3	TSL:1 MANE Select	c.517C>T	p.Pro173Ser	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.517C>T	p.Pro173Ser	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes AF: 0.0000405 AC: 6 AN: 148084 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000588

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000501 AC: 5 AN: 998538 Hom.: 0 Cov.: 31 AF XY: 0.00000425 AC XY: 2 AN XY: 470102

African (AFR) AF: 0.00 AC: 0 AN: 19928

American (AMR) AF: 0.00 AC: 0 AN: 5812

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10654

East Asian (EAS) AF: 0.000108 AC: 2 AN: 18520

South Asian (SAS) AF: 0.000106 AC: 2 AN: 18796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2454

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 867606

Other (OTH) AF: 0.0000266 AC: 1 AN: 37560

GnomAD4 genome AF: 0.0000337 AC: 5 AN: 148192 Hom.: 0 Cov.: 32 AF XY: 0.0000416 AC XY: 3 AN XY: 72180

African (AFR) AF: 0.00 AC: 0 AN: 41128

American (AMR) AF: 0.00 AC: 0 AN: 14948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3406

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5090

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66434

Other (OTH) AF: 0.00 AC: 0 AN: 2066

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.051
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0083	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.13
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.70	N
REVEL	Benign	0.024
Sift	Benign	0.80	T
Sift4G	Benign	0.81	T
Polyphen		0.0	B
Vest4		0.050
MutPred		0.19		Gain of phosphorylation at P173 (P = 0.0076)
MVP		0.088
ClinPred		0.049	T
GERP RS		-2.4
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.031
gMVP		0.24
Mutation Taster		=96/4	polymorphism

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: rs1298194314; hg19: chr1-27320794;