NM_001039615.3:c.698G>A

Variant names:

• chr8-12112953-G-A
• rs1442288872
• NM_001039615.3:c.698G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001039615.3(ZNF705D):​c.698G>A​(p.Cys233Tyr) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 7)
  • Exomes 𝑓: 0.000051 (6 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF705D NM_001039615.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

Genes affected

ZNF705D (HGNC:33202): (zinc finger protein 705D) 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039615.3. 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
	ZNF705D	NM_001039615.3	MANE Select	c.698G>A	p.Cys233Tyr	missense	Exon 7 of 7	NP_001034704.2	P0CH99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF705D	ENST00000400085.8	TSL:5 MANE Select	c.698G>A	p.Cys233Tyr	missense	Exon 7 of 7	ENSP00000382957.3	P0CH99

Frequencies

GnomAD3 genomes AF: 0.0000335 AC: 2 AN: 59614 Hom.: 0 Cov.: 7

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: 0.0000362

Gnomad OTH AF: 0.00168

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000510 AC: 56 AN: 1097924 Hom.: 6 Cov.: 21 AF XY: 0.0000435 AC XY: 24 AN XY: 551830

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

African (AFR) AF: 0.00 AC: 0 AN: 29838

American (AMR) AF: 0.00 AC: 0 AN: 29740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20484

East Asian (EAS) AF: 0.00 AC: 0 AN: 31900

South Asian (SAS) AF: 0.00 AC: 0 AN: 67788

European-Finnish (FIN) AF: 0.000161 AC: 7 AN: 43382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3122

European-Non Finnish (NFE) AF: 0.0000412 AC: 34 AN: 825148

Other (OTH) AF: 0.000322 AC: 15 AN: 46522

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000019984), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000335 AC: 2 AN: 59614 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 27740

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

African (AFR) AF: 0.00 AC: 0 AN: 21632

American (AMR) AF: 0.00 AC: 0 AN: 3606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1294

East Asian (EAS) AF: 0.00 AC: 0 AN: 1164

South Asian (SAS) AF: 0.00 AC: 0 AN: 942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2302

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 68

European-Non Finnish (NFE) AF: 0.0000362 AC: 1 AN: 27660

Other (OTH) AF: 0.00168 AC: 1 AN: 596

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

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	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0084	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	4.3	H
PhyloP100		4.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.56
MutPred		0.81		Loss of disorder (P = 0.0663)
MVP		0.60
ClinPred		0.45	T
GERP RS		1.0
Varity_R		0.42
gMVP		0.047
Mutation Taster		=84/16	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: rs1442288872; hg19: chr8-11970462;