4-85829-G-A

Position:

• chr4-85829-G-A

Variant summary

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

The NM_182524.4(ZNF595):​c.325G>A​(p.Glu109Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF595 NM_182524.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.210

Genes affected

ZNF595 (HGNC:27196): (zinc finger protein 595) This gene encodes a protein belonging to the Cys2His2 zinc finger protein family, whose members function as transcription factors that can regulate a broad variety of developmental and cellular processes. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Oct 2013]

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=0.1547367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF595	NM_182524.4	c.325G>A	p.Glu109Lys	missense_variant	4/4	ENST00000610261.6	NP_872330.1
ZNF595	NM_001286052.2	c.229G>A	p.Glu77Lys	missense_variant	3/3		NP_001272981.1
ZNF595	NM_001286053.2	c.-225G>A		5_prime_UTR_variant	2/2		NP_001272982.1
ZNF595	NM_001286054.2	c.-225G>A		5_prime_UTR_variant	5/5		NP_001272983.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF595	ENST00000610261.6	c.325G>A	p.Glu109Lys	missense_variant	4/4	1	NM_182524.4	ENSP00000477392	P1
ZNF595	ENST00000609518.5	c.229G>A	p.Glu77Lys	missense_variant	3/3	2		ENSP00000476408
ZNF595	ENST00000608255.2	c.-225G>A		5_prime_UTR_variant	2/2	2		ENSP00000476367

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 28, 2023

The c.325G>A (p.E109K) alteration is located in exon 4 (coding exon 4) of the ZNF595 gene. This alteration results from a G to A substitution at nucleotide position 325, causing the glutamic acid (E) at amino acid position 109 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	Benign	0.074
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	0.56
DANN	Benign	0.71
DEOGEN2	Benign	0.030	T;.
FATHMM_MKL	Benign	0.00030	N
LIST_S2	Benign	0.71	T;T
MetaRNN	Benign	0.15	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.029	B;.
Vest4		0.27
MVP		0.21
GERP RS		1.1
Varity_R		0.025
gMVP		0.055

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: chr4-85720;