chr8-12113114-C-T

Variant names:

• chr8-12113114-C-T
• rs1188950060
• NM_001039615.3:c.859C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039615.3(ZNF705D):​c.859C>T​(p.Leu287Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000016 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000079 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF705D NM_001039615.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.23
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.108929455).

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.859C>T	p.Leu287Phe	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.859C>T	p.Leu287Phe	missense	Exon 7 of 7	ENSP00000382957.3	P0CH99

Frequencies

GnomAD3 genomes AF: 0.0000164 AC: 2 AN: 122290 Hom.: 0 Cov.: 17

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: 0.0000361

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000787 AC: 102 AN: 1295288 Hom.: 15 Cov.: 30 AF XY: 0.0000915 AC XY: 59 AN XY: 644458

⚠️ 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: 32504

American (AMR) AF: 0.00 AC: 0 AN: 34964

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23110

East Asian (EAS) AF: 0.00 AC: 0 AN: 34176

South Asian (SAS) AF: 0.00 AC: 0 AN: 76750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3718

European-Non Finnish (NFE) AF: 0.0000999 AC: 99 AN: 990814

Other (OTH) AF: 0.0000559 AC: 3 AN: 53656

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000164 AC: 2 AN: 122290 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 58682

⚠️ 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: 37448

American (AMR) AF: 0.00 AC: 0 AN: 10076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2784

East Asian (EAS) AF: 0.00 AC: 0 AN: 3424

South Asian (SAS) AF: 0.00 AC: 0 AN: 3368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000361 AC: 2 AN: 55450

Other (OTH) AF: 0.00 AC: 0 AN: 1558

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), 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	Benign	0.11
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-1.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.036
Sift	Benign	0.71	T
Sift4G	Benign	0.065	T
Polyphen		0.99	D
Vest4		0.19
MutPred		0.36		Gain of methylation at K291 (P = 0.0855)
MVP		0.055
ClinPred		0.42	T
GERP RS		0.74
Varity_R		0.039
gMVP		0.0083
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: rs1188950060; hg19: chr8-11970623;