17-75815253-C-T

Variant summary

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

The NM_001080419.3(UNK):​c.961C>T​(p.Gln321*) variant causes a stop gained, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

UNK
NM_001080419.3 stop_gained, splice_region

Scores

4
2
2
Splicing: ADA: 0.9951
2

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.07
Variant links:
Genes affected
UNK (HGNC:29369): (unk zinc finger) Enables mRNA CDS binding activity. Involved in cell morphogenesis involved in neuron differentiation and negative regulation of cytoplasmic translation. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UNKNM_001080419.3 linkc.961C>T p.Gln321* stop_gained, splice_region_variant Exon 7 of 16 ENST00000589666.6 NP_001073888.2 Q9C0B0A0A024R8N4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UNKENST00000589666.6 linkc.961C>T p.Gln321* stop_gained, splice_region_variant Exon 7 of 16 1 NM_001080419.3 ENSP00000464893.1 Q9C0B0
UNKENST00000586217.1 linkn.*475C>T downstream_gene_variant 3 ENSP00000466054.1 K7ELF5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
Jan 11, 2021
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

Gene of uncertain clinical significance -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.55
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
43
DANN
Uncertain
1.0
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Uncertain
0.90
D
M_CAP
Benign
0.0021
T
Vest4
0.86
GERP RS
5.0

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.83
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: chr17-73811334; COSMIC: COSV53147232; COSMIC: COSV53147232; API