1-26993916-C-T

Variant names:

• chr1-26993916-C-T
• rs773839746
• NM_001013642.3:c.130C>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.130C>T​(p.Pro44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000821 in 1,217,578 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. 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. P44A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: TRNP1 NM_001013642.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.512
• 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=0.029809862).

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.130C>T	p.Pro44Ser	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.130C>T	p.Pro44Ser	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.130C>T	p.Pro44Ser	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.21e-7 AC: 1 AN: 1217578 Hom.: 0 Cov.: 34 AF XY: 0.00000168 AC XY: 1 AN XY: 593590

African (AFR) AF: 0.00 AC: 0 AN: 24160

American (AMR) AF: 0.00 AC: 0 AN: 10938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17882

East Asian (EAS) AF: 0.00 AC: 0 AN: 27514

South Asian (SAS) AF: 0.00 AC: 0 AN: 52694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4176

European-Non Finnish (NFE) AF: 9.99e-7 AC: 1 AN: 1001072

Other (OTH) AF: 0.00 AC: 0 AN: 49968

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.7
DANN	Benign	0.91
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.00093	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.51
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.015
Sift	Benign	0.81	T
Sift4G	Benign	0.10	T
Polyphen		0.0010	B
Vest4		0.052
MutPred		0.12		Gain of phosphorylation at P44 (P = 0.0162)
MVP		0.014
ClinPred		0.071	T
GERP RS		-1.7
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.028
gMVP		0.42
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs773839746; hg19: chr1-27320407;