19-23359620-G-C

Position:

• chr19-23359620-G-C

Variant summary

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

The NM_003430.4(ZNF91):​c.3359C>G​(p.Ala1120Gly) 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. 15/21 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)
• Consequence: ZNF91 NM_003430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.64

Genes affected

ZNF91 (HGNC:13166): (zinc finger protein 91) The ZNF91 gene encodes a zinc finger protein of the KRAB (Kruppel-associated box) subfamily (Bellefroid et al., 1991, 1993 [PubMed 2023909] [PubMed 8467795]).[supplied by OMIM, May 2010]

ZNF91 (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=0.13562322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF91	NM_003430.4	c.3359C>G	p.Ala1120Gly	missense_variant	4/4	ENST00000300619.12	NP_003421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF91	ENST00000300619.12	c.3359C>G	p.Ala1120Gly	missense_variant	4/4	1	NM_003430.4	ENSP00000300619.6
ZNF91	ENST00000397082.2	c.3263C>G	p.Ala1088Gly	missense_variant	3/3	2		ENSP00000380272.2
ZNF91	ENST00000599743.5	c.253+14122C>G		intron_variant		3		ENSP00000468867.1
ZNF91	ENST00000596989.1	n.370+14122C>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

EpiCase AF: 0.000109

EpiControl AF: 0.00

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 06, 2024

The c.3359C>G (p.A1120G) alteration is located in exon 4 (coding exon 4) of the ZNF91 gene. This alteration results from a C to G substitution at nucleotide position 3359, causing the alanine (A) at amino acid position 1120 to be replaced by a glycine (G). 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	0.25
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.5
DANN	Benign	0.80
DEOGEN2	Benign	0.0026	T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.12	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.30	N;N
REVEL	Benign	0.039
Sift	Benign	0.46	T;T
Sift4G	Benign	0.49	T;T
Polyphen		0.81	P;P
Vest4		0.047
MutPred		0.27		Loss of stability (P = 0.0455);.;
MVP		0.27
MPC		0.43
ClinPred		0.12	T
GERP RS		0.19
Varity_R		0.024
gMVP		0.011

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: rs1599718969; hg19: chr19-23542422;