rs757121645

Variant names:

• chr19-53402155-G-A
• rs757121645
• NM_001040185.3:c.106G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-53402155-G-A
• chr19-53402155-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001350496.2(ZNF765-ZNF761):​c.-1381G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,613,814 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000069 (1 hom.)
• Consequence: ZNF765-ZNF761 NM_001350496.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.31
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350496.2. 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.106G>A	p.Val36Met	missense	Exon 3 of 4	NP_001035275.1	Q7L2R6-1
	ZNF765-ZNF761	NM_001350496.2		c.-1381G>A		5_prime_UTR_premature_start_codon_gain	Exon 3 of 13	NP_001337425.1
	ZNF765-ZNF761	NM_001350496.2		c.-1381G>A		5_prime_UTR	Exon 3 of 13	NP_001337425.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF765	ENST00000396408.8	TSL:1 MANE Select	c.106G>A	p.Val36Met	missense	Exon 3 of 4	ENSP00000379689.3	Q7L2R6-1
	ZNF765	ENST00000504235.5	TSL:1	n.106G>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000424395.1	Q7L2R6-2
	ZNF765	ENST00000933978.1		c.106G>A	p.Val36Met	missense	Exon 2 of 3	ENSP00000604037.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152060 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000319 AC: 8 AN: 250578 AF XY: 0.0000516

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: 0.0000706

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000691 AC: 101 AN: 1461754 Hom.: 1 Cov.: 34 AF XY: 0.0000701 AC XY: 51 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86232

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000863 AC: 96 AN: 1111958

Other (OTH) AF: 0.0000331 AC: 2 AN: 60390

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152060 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74262

African (AFR) AF: 0.00 AC: 0 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000864 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	Pathogenic	0.61
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Benign	0.046
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0012	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		3.3
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.17
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.016	D
Polyphen		0.90	P
Vest4		0.52
MutPred		0.82		Gain of helix (P = 0.1736)
MVP		0.26
MPC		0.21
ClinPred		0.46	T
GERP RS		1.6
Varity_R		0.099
gMVP		0.11
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs757121645; hg19: chr19-53905408;