chr16-31753826-A-C

Position:

• chr16-31753826-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001130913.2(KRBOX5):​c.287A>C​(p.Gln96Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,396,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: KRBOX5 NM_001130913.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0110

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1351963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRBOX5	NM_001130913.2	c.287A>C	p.Gln96Pro	missense_variant	4/5	ENST00000316491.14	NP_001124385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRBOX5	ENST00000316491.14	c.287A>C	p.Gln96Pro	missense_variant	4/5	1	NM_001130913.2	ENSP00000319222.9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000931 AC: 13 AN: 1396198 Hom.: 0 Cov.: 30 AF XY: 0.0000102 AC XY: 7 AN XY: 688592

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: 0.00000928

Gnomad4 OTH exome AF: 0.0000519

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Oct 01, 2024

The c.287A>C (p.Q96P) alteration is located in exon 4 (coding exon 4) of the ZNF720 gene. This alteration results from a A to C substitution at nucleotide position 287, causing the glutamine (Q) at amino acid position 96 to be replaced by a proline (P). 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	0.088
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.9
DANN	Benign	0.48
DEOGEN2	Benign	0.091	.;T;.;.;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.51	T;T;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.2	.;L;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-4.4	D;D;D;D;D
REVEL	Benign	0.13
Sift	Benign	0.28	T;T;T;T;T
Sift4G	Pathogenic	0.0	D;T;D;T;T
Polyphen		0.26, 0.96	.;B;D;.;.
Vest4		0.42
MVP		0.15
MPC		0.68
ClinPred		0.29	T
GERP RS		0.67
Varity_R		0.42

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

LitVar

Other links and lift over

dbSNP: rs909477537; hg19: chr16-31765147;