19-23359485-A-C

Variant names:

• chr19-23359485-A-C
• rs1365880553
• NM_003430.4:c.3494T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003430.4(ZNF91):​c.3494T>G​(p.Leu1165Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,609,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ZNF91 NM_003430.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.595
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18054241).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003430.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF91	NM_003430.4	MANE Select	c.3494T>G	p.Leu1165Arg	missense	Exon 4 of 4	NP_003421.2	Q05481-1
	ZNF91	NM_001300951.2		c.3398T>G	p.Leu1133Arg	missense	Exon 3 of 3	NP_001287880.1	Q05481-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF91	ENST00000300619.12	TSL:1 MANE Select	c.3494T>G	p.Leu1165Arg	missense	Exon 4 of 4	ENSP00000300619.6	Q05481-1
	ZNF91	ENST00000909304.1		c.3473T>G	p.Leu1158Arg	missense	Exon 4 of 4	ENSP00000579363.1
	ZNF91	ENST00000397082.2	TSL:2	c.3398T>G	p.Leu1133Arg	missense	Exon 3 of 3	ENSP00000380272.2	Q05481-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 151978 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248886 AF XY: 0.0000296

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1457398 Hom.: 0 Cov.: 27 AF XY: 0.0000110 AC XY: 8 AN XY: 725348

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.0000448 AC: 2 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108024

Other (OTH) AF: 0.0000166 AC: 1 AN: 60246

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 151978 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74218

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.000131 AC: 2 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000248 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	13
DANN	Benign	0.61
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.59
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.028
Sift	Benign	0.75	T
Sift4G	Benign	0.15	T
Polyphen		0.016	B
Vest4		0.20
MutPred		0.40		Gain of disorder (P = 0.0381)
MVP		0.10
MPC		0.29
ClinPred		0.042	T
Varity_R		0.17
gMVP		0.024
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1365880553; hg19: chr19-23542287;