chr17-75823323-G-A

Variant names:

• chr17-75823323-G-A
• rs2062086520
• NM_001080419.3:c.2078G>A

Variant summary

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

The NM_001080419.3(UNK):​c.2078G>A​(p.Gly693Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UNK NM_001080419.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

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]

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=0.08072981).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNK	NM_001080419.3	c.2078G>A	p.Gly693Asp	missense_variant	Exon 15 of 16	ENST00000589666.6	NP_001073888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNK	ENST00000589666.6	c.2078G>A	p.Gly693Asp	missense_variant	Exon 15 of 16	1	NM_001080419.3	ENSP00000464893.1
UNK	ENST00000587258.1	c.392G>A	p.Gly131Asp	missense_variant	Exon 4 of 5	5		ENSP00000467726.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 24, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2078G>A (p.G693D) alteration is located in exon 15 (coding exon 15) of the UNK gene. This alteration results from a G to A substitution at nucleotide position 2078, causing the glycine (G) at amino acid position 693 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		2.2
PrimateAI	Uncertain	0.58	T
Sift4G	Benign	0.60	T
Polyphen		0.043	B
Vest4		0.34
MutPred		0.27		Gain of helix (P = 0.0082);
MVP		0.043
MPC		0.59
ClinPred		0.89	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.094
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2062086520; hg19: chr17-73819404;