8-143649891-G-T

Position:

• chr8-143649891-G-T

Variant summary

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

The NM_001261843.2(ZNF623):​c.-95-7G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,450,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ZNF623 NM_001261843.2 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.49

Genes affected

ZNF623 (HGNC:29084): (zinc finger protein 623) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.06880078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF623	NM_001261843.2	c.-95-7G>T		splice_region_variant, intron_variant		ENST00000526926.6	NP_001248772.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF623	ENST00000526926.6	c.-95-7G>T		splice_region_variant, intron_variant		2	NM_001261843.2	ENSP00000435232.1
ZNF623	ENST00000458270.2	c.-95-7G>T		splice_region_variant, intron_variant		1		ENSP00000411139.2
ZNF623	ENST00000501748.3	c.19G>T	p.Val7Phe	missense_variant	1/1	6		ENSP00000445979.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000138 AC: 20 AN: 1450144 Hom.: 0 Cov.: 34 AF XY: 0.0000153 AC XY: 11 AN XY: 719182

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: 0.0000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

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

Aug 08, 2023

The c.19G>T (p.V7F) alteration is located in exon 1 (coding exon 1) of the ZNF623 gene. This alteration results from a G to T substitution at nucleotide position 19, causing the valine (V) at amino acid position 7 to be replaced by a phenylalanine (F). 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	0.083
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0056	N
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.043
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.11	T
Vest4		0.057
MutPred		0.43		Loss of sheet (P = 0.0084);
MVP		0.092
MPC		0.37
ClinPred		0.058	T
GERP RS		-3.2
gMVP		0.10

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

Publications

LitVar

Other links and lift over

dbSNP: rs764701382; hg19: chr8-144732061;