16-1367292-C-G

Position:

• chr16-1367292-C-G

Variant summary

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

The NM_001372107.1(UNKL):​c.1846G>C​(p.Asp616His) variant causes a missense change. 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: UNKL NM_001372107.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

Genes affected

UNKL (HGNC:14184): (unk like zinc finger) This gene encodes a RING finger protein that may function in Rac signaling. It can bind to Brg/Brm-associated factor 60b and can promote its ubiquitination. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jun 2013]

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/exons	MANE	UniProt
UNKL	NM_001372107.1	c.1846G>C	p.Asp616His	missense_variant	14/15	ENST00000389221.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UNKL	ENST00000389221.9	c.1846G>C	p.Asp616His	missense_variant	14/15	5	NM_001372107.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.1837G>C (p.D613H) alteration is located in exon 14 (coding exon 14) of the UNKL gene. This alteration results from a G to C substitution at nucleotide position 1837, causing the aspartic acid (D) at amino acid position 613 to be replaced by a histidine (H). 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
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Uncertain	0.21	D
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.2	D;.;D;N
REVEL	Benign	0.28
Sift	Uncertain	0.021	D;.;D;T
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.48
MutPred		0.27		.;Gain of MoRF binding (P = 0.051);.;Gain of MoRF binding (P = 0.051);
MVP		0.87
MPC		0.35
ClinPred		0.94	D
GERP RS		5.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1390054794; hg19: chr16-1417293; COSMIC: COSV99201731; COSMIC: COSV99201731;