rs8182488

Variant names:

• chr19-53408257-G-A
• rs8182488
• NM_001040185.3:c.702G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-53408257-G-A
• chr19-53408257-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001040185.3(ZNF765):​c.702G>A​(p.Gln234Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,614,056 control chromosomes in the GnomAD database, including 89,951 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (6545 hom., cov: 33)
  • Exomes 𝑓: 0.33 (83406 hom.)
• Consequence: ZNF765 NM_001040185.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 17 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=0.389 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF765	NM_001040185.3	c.702G>A	p.Gln234Gln	synonymous_variant	Exon 4 of 4	ENST00000396408.8	NP_001035275.1
ZNF765	NM_001350495.2	c.543G>A	p.Gln181Gln	synonymous_variant	Exon 3 of 3		NP_001337424.1
ZNF765-ZNF761	NM_001350496.2	c.-1345+6066G>A		intron_variant	Intron 3 of 12		NP_001337425.1
ZNF765	NR_146721.2	n.260+6066G>A		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF765	ENST00000396408.8	c.702G>A	p.Gln234Gln	synonymous_variant	Exon 4 of 4	1	NM_001040185.3	ENSP00000379689.3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40209 AN: 152078 Hom.: 6535 Cov.: 33

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.256

GnomAD2 exomes AF: 0.320 AC: 80364 AN: 250966 AF XY: 0.323

Gnomad AFR exome AF: 0.0816

Gnomad AMR exome AF: 0.439

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.101

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.330 AC: 483074 AN: 1461860 Hom.: 83406 Cov.: 65 AF XY: 0.332 AC XY: 241107 AN XY: 727230

African (AFR) AF: 0.0814 AC: 2725 AN: 33478

American (AMR) AF: 0.429 AC: 19201 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5725 AN: 26132

East Asian (EAS) AF: 0.0857 AC: 3404 AN: 39698

South Asian (SAS) AF: 0.375 AC: 32361 AN: 86250

European-Finnish (FIN) AF: 0.376 AC: 20087 AN: 53420

Middle Eastern (MID) AF: 0.262 AC: 1511 AN: 5768

European-Non Finnish (NFE) AF: 0.341 AC: 379695 AN: 1111994

Other (OTH) AF: 0.304 AC: 18365 AN: 60396

GnomAD4 genome AF: 0.264 AC: 40248 AN: 152196 Hom.: 6545 Cov.: 33 AF XY: 0.267 AC XY: 19889 AN XY: 74386

African (AFR) AF: 0.0921 AC: 3824 AN: 41538

American (AMR) AF: 0.349 AC: 5342 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3472

East Asian (EAS) AF: 0.0987 AC: 512 AN: 5186

South Asian (SAS) AF: 0.372 AC: 1798 AN: 4828

European-Finnish (FIN) AF: 0.367 AC: 3876 AN: 10574

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23151 AN: 67988

Other (OTH) AF: 0.256 AC: 541 AN: 2114

Alfa AF: 0.303 Hom.: 3607

Bravo AF: 0.250

Asia WGS AF: 0.251 AC: 870 AN: 3478

EpiCase AF: 0.323

EpiControl AF: 0.320

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.86
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs8182488; hg19: chr19-53911510; COSMIC: COSV67182579; COSMIC: COSV67182579;