rs2023400635

Variant names:

• chr19-12624652-G-A
• rs2023400635
• NM_153358.3:c.133G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_153358.3(ZNF791):​c.133G>A​(p.Glu45Lys) variant causes a missense, splice region 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. 16/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: ZNF791 NM_153358.3 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 0 publications found

Genes affected

ZNF791 (HGNC:26895): (zinc finger protein 791) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF490 (HGNC:23705): (zinc finger protein 490) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03230405).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153358.3. 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
	ZNF791	NM_153358.3	MANE Select	c.133G>A	p.Glu45Lys	missense splice_region	Exon 3 of 4	NP_699189.2	Q3KP31-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF791	ENST00000343325.9	TSL:1 MANE Select	c.133G>A	p.Glu45Lys	missense splice_region	Exon 3 of 4	ENSP00000342974.4	Q3KP31-1
	ZNF791	ENST00000446165.2	TSL:1	c.130+826G>A		intron	N/A	ENSP00000412981.1	C9JU55
	ZNF791	ENST00000600752.1	TSL:2	c.-195G>A		splice_region	Exon 2 of 3	ENSP00000471179.1	M0R0E8

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

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	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.20
DANN	Benign	0.78
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.00053	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.90	N
PhyloP100		-1.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.88	N
REVEL	Benign	0.034
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.40		Gain of ubiquitination at E45 (P = 0.0131)
MVP		0.11
MPC		0.39
ClinPred		0.042	T
GERP RS		-3.0
Varity_R		0.015
gMVP		0.078
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: rs2023400635; hg19: chr19-12735466;