chr1-26993886-C-A

Variant names:

• chr1-26993886-C-A
• rs1238754589
• NM_001013642.3:c.100C>A

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.100C>A​(p.Gln34Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,374,426 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TRNP1 NM_001013642.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0330
• 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=0.1448142).

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.100C>A	p.Gln34Lys	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.100C>A	p.Gln34Lys	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.100C>A	p.Gln34Lys	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152070 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: 0.00

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: 0.00 AC: 0 AN: 15094 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000409 AC: 5 AN: 1222356 Hom.: 0 Cov.: 34 AF XY: 0.00000336 AC XY: 2 AN XY: 595200

African (AFR) AF: 0.00 AC: 0 AN: 24296

American (AMR) AF: 0.00 AC: 0 AN: 11990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18036

East Asian (EAS) AF: 0.00 AC: 0 AN: 27516

South Asian (SAS) AF: 0.00 AC: 0 AN: 53622

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3898

European-Non Finnish (NFE) AF: 0.00000498 AC: 5 AN: 1003204

Other (OTH) AF: 0.00 AC: 0 AN: 50414

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74266

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.33	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.033
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.041
Sift	Benign	1.0	T
Sift4G	Benign	0.82	T
Polyphen		0.072	B
Vest4		0.15
MutPred		0.26		Gain of methylation at Q34 (P = 6e-04)
MVP		0.076
ClinPred		0.67	D
GERP RS		3.5
PromoterAI		-0.073	Neutral
Varity_R		0.18
gMVP		0.17
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: rs1238754589; hg19: chr1-27320377;