1-26994073-C-T

Variant names:

• chr1-26994073-C-T
• rs1383608505
• NM_001013642.3:c.287C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013642.3(TRNP1):​c.287C>T​(p.Ala96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000329 in 1,215,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: TRNP1 NM_001013642.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1303756).

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.287C>T	p.Ala96Val	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.287C>T	p.Ala96Val	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.287C>T	p.Ala96Val	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes AF: 0.0000200 AC: 3 AN: 149922 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 9.39e-7 AC: 1 AN: 1065188 Hom.: 0 Cov.: 34 AF XY: 0.00000198 AC XY: 1 AN XY: 504372

African (AFR) AF: 0.00 AC: 0 AN: 22082

American (AMR) AF: 0.000131 AC: 1 AN: 7660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13288

East Asian (EAS) AF: 0.00 AC: 0 AN: 24626

South Asian (SAS) AF: 0.00 AC: 0 AN: 20208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2802

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 911510

Other (OTH) AF: 0.00 AC: 0 AN: 42158

GnomAD4 genome AF: 0.0000200 AC: 3 AN: 150030 Hom.: 0 Cov.: 32 AF XY: 0.0000273 AC XY: 2 AN XY: 73336

African (AFR) AF: 0.00 AC: 0 AN: 41028

American (AMR) AF: 0.000132 AC: 2 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.000198 AC: 1 AN: 5038

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67208

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.58	N
REVEL	Benign	0.090
Sift	Benign	0.061	T
Sift4G	Uncertain	0.057	T
Polyphen		0.98	D
Vest4		0.11
MutPred		0.20		Loss of helix (P = 0.0444)
MVP		0.014
ClinPred		0.32	T
GERP RS		2.1
PromoterAI		0.034	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		4.7
Varity_R		0.039
gMVP		0.23
Mutation Taster		=86/14	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: rs1383608505; hg19: chr1-27320564;