19-53407838-C-G

Variant names:

• chr19-53407838-C-G
• rs746730483
• NM_001040185.3:c.283C>G

Variant summary

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

The NM_001040185.3(ZNF765):​c.283C>G​(p.His95Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. H95N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF765 NM_001040185.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 1 publications found

Genes affected

ZNF765 (HGNC:25092): (zinc finger protein 765) 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]

ZNF765-ZNF761 (HGNC:):

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=0.16844717).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040185.3. 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
	ZNF765	NM_001040185.3	MANE Select	c.283C>G	p.His95Asp	missense	Exon 4 of 4	NP_001035275.1	Q7L2R6-1
	ZNF765	NM_001350495.2		c.124C>G	p.His42Asp	missense	Exon 3 of 3	NP_001337424.1
	ZNF765-ZNF761	NM_001350496.2		c.-1345+5647C>G		intron	N/A	NP_001337425.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF765	ENST00000396408.8	TSL:1 MANE Select	c.283C>G	p.His95Asp	missense	Exon 4 of 4	ENSP00000379689.3	Q7L2R6-1
	ZNF765	ENST00000504235.5	TSL:1	n.142+5647C>G		intron	N/A	ENSP00000424395.1	Q7L2R6-2
	ZNF765	ENST00000933978.1		c.283C>G	p.His95Asp	missense	Exon 3 of 3	ENSP00000604037.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249602 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

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: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461210 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726850

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111806

Other (OTH) AF: 0.00 AC: 0 AN: 60368

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.7
DANN	Benign	0.75
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-2.0
PROVEAN	Pathogenic	-7.9	D
REVEL	Benign	0.024
Sift	Uncertain	0.029	D
Sift4G	Benign	0.095	T
Polyphen		0.91	P
Vest4		0.15
MutPred		0.24		Gain of disorder (P = 0.0608)
MVP		0.14
MPC		0.18
ClinPred		0.33	T
GERP RS		0.072
Varity_R		0.16
gMVP		0.026
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: rs746730483; hg19: chr19-53911091;