19-23359483-A-G

Variant names:

• chr19-23359483-A-G
• rs760312253
• NM_003430.4:c.3496T>C

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.3496T>C​(p.Trp1166Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZNF91 NM_003430.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• 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=0.09331021).

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.3496T>C	p.Trp1166Arg	missense	Exon 4 of 4	NP_003421.2	Q05481-1
	ZNF91	NM_001300951.2		c.3400T>C	p.Trp1134Arg	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.3496T>C	p.Trp1166Arg	missense	Exon 4 of 4	ENSP00000300619.6	Q05481-1
	ZNF91	ENST00000909304.1		c.3475T>C	p.Trp1159Arg	missense	Exon 4 of 4	ENSP00000579363.1
	ZNF91	ENST00000397082.2	TSL:2	c.3400T>C	p.Trp1134Arg	missense	Exon 3 of 3	ENSP00000380272.2	Q05481-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248712 AF XY: 0.00

Gnomad AFR exome AF: 0.0000649

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459054 Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1 AN XY: 726032

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109554

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000331 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.3
DANN	Benign	0.25
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.56
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.023
Sift	Benign	0.78	T
Sift4G	Benign	0.81	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.47		Gain of disorder (P = 0.0082)
MVP		0.19
MPC		0.35
ClinPred		0.012	T
Varity_R		0.15
gMVP		0.019
Mutation Taster		=99/1	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: rs760312253; hg19: chr19-23542285;