16-31723266-G-C

Position:

• chr16-31723266-G-C

Variant summary

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

The NM_001130913.2(KRBOX5):​c.139G>C​(p.Val47Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KRBOX5 NM_001130913.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.544

Genes affected

KRBOX5 (HGNC:26987): (KRAB box domain containing 5) Predicted to be involved in regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

KRBOX5 (HGNC:):

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	Protein	UniProt
KRBOX5	NM_001130913.2	c.139G>C	p.Val47Leu	missense_variant	3/5	ENST00000316491.14	NP_001124385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRBOX5	ENST00000316491.14	c.139G>C	p.Val47Leu	missense_variant	3/5	1	NM_001130913.2	ENSP00000319222.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461384 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726942

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Dec 02, 2022

The c.139G>C (p.V47L) alteration is located in exon 3 (coding exon 3) of the ZNF720 gene. This alteration results from a G to C substitution at nucleotide position 139, causing the valine (V) at amino acid position 47 to be replaced by a leucine (L). 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	0.22
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;.;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.025	T;T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.024
Sift	Benign	0.066	T;D;T
Sift4G	Benign	0.13	T;T;T
Polyphen		0.043	B;.;.
Vest4		0.12
MutPred		0.43		Loss of methylation at K49 (P = 0.087);.;Loss of methylation at K49 (P = 0.087);
MVP		0.014
MPC		0.17
ClinPred		0.079	T
GERP RS		1.5
Varity_R		0.051

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.33		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.33		Position offset: 9

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: chr16-31734587;