4-85892-A-T

Position:

• chr4-85892-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_182524.4(ZNF595):​c.388A>T​(p.Asn130Tyr) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF595 NM_182524.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.98

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071742326).
• BP6: Variant 4-85892-A-T is Benign according to our data. Variant chr4-85892-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2537494.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF595	NM_182524.4	c.388A>T	p.Asn130Tyr	missense_variant	4/4	ENST00000610261.6	NP_872330.1
ZNF595	NM_001286052.2	c.292A>T	p.Asn98Tyr	missense_variant	3/3		NP_001272981.1
ZNF595	NM_001286053.2	c.-162A>T		5_prime_UTR_variant	2/2		NP_001272982.1
ZNF595	NM_001286054.2	c.-162A>T		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.388A>T	p.Asn130Tyr	missense_variant	4/4	1	NM_182524.4	ENSP00000477392	P1
ZNF595	ENST00000609518.5	c.292A>T	p.Asn98Tyr	missense_variant	3/3	2		ENSP00000476408
ZNF595	ENST00000608255.2	c.-162A>T		5_prime_UTR_variant	2/2	2		ENSP00000476367

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	0.018
DANN	Benign	0.57
DEOGEN2	Benign	0.0036	T;.
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Benign	0.0072	T;T
MetaRNN	Benign	0.072	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;.
Vest4		0.080
MVP		0.088
GERP RS		-1.7
Varity_R		0.034
gMVP		0.029

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: rs782668166; hg19: chr4-85783;