chr19-23360468-G-C

Position:

• chr19-23360468-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003430.4(ZNF91):​c.2511C>G​(p.His837Gln) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: ZNF91 NM_003430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -9.52

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]

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=0.03670183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF91	NM_003430.4	c.2511C>G	p.His837Gln	missense_variant	4/4	ENST00000300619.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF91	ENST00000300619.12	c.2511C>G	p.His837Gln	missense_variant	4/4	1	NM_003430.4	P1
ZNF91	ENST00000397082.2	c.2415C>G	p.His805Gln	missense_variant	3/3	2
ZNF91	ENST00000599743.5	c.253+13274C>G		intron_variant		3
ZNF91	ENST00000596989.1	n.370+13274C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 80

GnomAD4 genome Cov.: 34

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

Apr 23, 2024

The c.2511C>G (p.H837Q) 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 2511, causing the histidine (H) at amino acid position 837 to be replaced by a glutamine (Q). 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	0.26
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0050
DANN	Benign	0.085
DEOGEN2	Benign	0.00046	T;.
Eigen	Benign	-2.8
Eigen_PC	Benign	-2.9
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.024	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.037	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.67	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.0040
Sift	Benign	0.56	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.012	B;B
Vest4		0.023
MutPred		0.23		Gain of catalytic residue at H837 (P = 0.0609);.;
MVP		0.15
MPC		0.33
ClinPred		0.019	T
GERP RS		-3.0
Varity_R		0.028
gMVP		0.0092

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: chr19-23543270;