17-75812135-C-A

Variant names:

• chr17-75812135-C-A
• NM_001080419.3:c.338C>A

Variant summary

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

The NM_001080419.3(UNK):​c.338C>A​(p.Thr113Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.91

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

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
UNK	NM_001080419.3	c.338C>A	p.Thr113Lys	missense_variant	Exon 3 of 16	ENST00000589666.6	NP_001073888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNK	ENST00000589666.6	c.338C>A	p.Thr113Lys	missense_variant	Exon 3 of 16	1	NM_001080419.3	ENSP00000464893.1
UNK	ENST00000592629.1	n.*304C>A		non_coding_transcript_exon_variant	Exon 4 of 4	3		ENSP00000466431.1
UNK	ENST00000592629.1	n.*304C>A		3_prime_UTR_variant	Exon 4 of 4	3		ENSP00000466431.1
UNK	ENST00000586217.1	n.-14C>A		upstream_gene_variant		3		ENSP00000466054.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.338C>A (p.T113K) alteration is located in exon 3 (coding exon 3) of the UNK gene. This alteration results from a C to A substitution at nucleotide position 338, causing the threonine (T) at amino acid position 113 to be replaced by a lysine (K). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Pathogenic	0.87	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.95	P
Vest4		0.71
MutPred		0.30		Gain of ubiquitination at T113 (P = 0.0138);
MVP		0.10
MPC		1.8
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.44
gMVP		0.86

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: chr17-73808216;