3-39143101-A-T

Variant names:

• chr3-39143101-A-T
• NM_033027.4:c.1724T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033027.4(CSRNP1):​c.1724T>A​(p.Phe575Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CSRNP1 NM_033027.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.47

Genes affected

CSRNP1 (HGNC:14300): (cysteine and serine rich nuclear protein 1) This gene encodes a protein that localizes to the nucleus and expression of this gene is induced in response to elevated levels of axin. The Wnt signalling pathway, which is negatively regulated by axin, is important in axis formation in early development and impaired regulation of this signalling pathway is often involved in tumors. A decreased level of expression of this gene in tumors compared to the level of expression in their corresponding normal tissues suggests that this gene product has a tumor suppressor function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25778532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSRNP1	NM_033027.4	c.1724T>A	p.Phe575Tyr	missense_variant	Exon 5 of 5	ENST00000273153.10	NP_149016.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSRNP1	ENST00000273153.10	c.1724T>A	p.Phe575Tyr	missense_variant	Exon 5 of 5	1	NM_033027.4	ENSP00000273153.5
CSRNP1	ENST00000514182.1	c.1724T>A	p.Phe575Tyr	missense_variant	Exon 5 of 5	1		ENSP00000422532.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456890 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723736

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.058
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.34	.;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.53	N;N
REVEL	Benign	0.12
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.88	P;P
Vest4		0.29
MutPred		0.28		Gain of glycosylation at T578 (P = 0.1182);Gain of glycosylation at T578 (P = 0.1182);
MVP		0.44
MPC		0.77
ClinPred		0.75	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-39184592;