rs3989699

Variant names:

• chr8-7361099-C-G
• rs3989699
• NM_001164457.3:c.139+11G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-7361099-C-G
• chr8-7361099-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001164457.3(ZNF705G):​c.139+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (5395 hom., cov: 38)
  • Exomes 𝑓: 0.35 (8899 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF705G NM_001164457.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0490
• Publications: 3 publications found

Genes affected

ZNF705G (HGNC:37134): (zinc finger protein 705G) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 8-7361099-C-G is Benign according to our data. Variant chr8-7361099-C-G is described in ClinVar as Benign. ClinVar VariationId is 403627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF705G	NM_001164457.3	c.139+11G>C		intron_variant	Intron 4 of 6	ENST00000400156.4	NP_001157929.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF705G	ENST00000400156.4	c.139+11G>C		intron_variant	Intron 4 of 6	2	NM_001164457.3	ENSP00000383020.4

Frequencies

GnomAD3 genomes AF: 0.400 AC: 58653 AN: 146736 Hom.: 5372 Cov.: 38

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.365

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.363 AC: 83776 AN: 230514 AF XY: 0.357

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.397

Gnomad EAS exome AF: 0.269

Gnomad FIN exome AF: 0.373

Gnomad NFE exome AF: 0.366

Gnomad OTH exome AF: 0.370

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.351 AC: 460821 AN: 1311408 Hom.: 8899 Cov.: 98 AF XY: 0.350 AC XY: 229419 AN XY: 655796

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.521 AC: 16440 AN: 31548

American (AMR) AF: 0.383 AC: 16644 AN: 43490

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 9957 AN: 25006

East Asian (EAS) AF: 0.270 AC: 10538 AN: 39096

South Asian (SAS) AF: 0.306 AC: 25188 AN: 82438

European-Finnish (FIN) AF: 0.376 AC: 14467 AN: 38472

Middle Eastern (MID) AF: 0.352 AC: 1384 AN: 3934

European-Non Finnish (NFE) AF: 0.349 AC: 346154 AN: 991542

Other (OTH) AF: 0.359 AC: 20049 AN: 55882

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.400 AC: 58726 AN: 146854 Hom.: 5395 Cov.: 38 AF XY: 0.399 AC XY: 28667 AN XY: 71818

African (AFR) AF: 0.503 AC: 19222 AN: 38186

American (AMR) AF: 0.382 AC: 5727 AN: 14990

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1373 AN: 3418

East Asian (EAS) AF: 0.270 AC: 1376 AN: 5088

South Asian (SAS) AF: 0.311 AC: 1454 AN: 4676

European-Finnish (FIN) AF: 0.383 AC: 3979 AN: 10378

Middle Eastern (MID) AF: 0.370 AC: 108 AN: 292

European-Non Finnish (NFE) AF: 0.364 AC: 24319 AN: 66860

Other (OTH) AF: 0.398 AC: 823 AN: 2066

Alfa AF: 0.315 Hom.: 132

Asia WGS AF: 0.325 AC: 1131 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.0
DANN	Benign	0.47
PhyloP100		-0.049
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: rs3989699; hg19: chr8-7218621; COSMIC: COSV67950347;