8-12113048-T-C

Variant names:

• chr8-12113048-T-C
• NM_001039615.3:c.793T>C
• ZNF705D p.Phe265Leu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001039615.3(ZNF705D):​c.793T>C​(p.Phe265Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 16)
  • Failed GnomAD Quality Control
• Consequence: ZNF705D NM_001039615.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.25
• 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.

• PM2: Very rare variant in population databases, with high coverage

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.793T>C	p.Phe265Leu	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.793T>C	p.Phe265Leu	missense	Exon 7 of 7	ENSP00000382957.3	P0CH99

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 115420 Hom.: 0 Cov.: 16

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 115420 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 55272

African (AFR) AF: 0.00 AC: 0 AN: 36038

American (AMR) AF: 0.00 AC: 0 AN: 9130

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2638

East Asian (EAS) AF: 0.00 AC: 0 AN: 3144

South Asian (SAS) AF: 0.00 AC: 0 AN: 3034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52534

Other (OTH) AF: 0.00 AC: 0 AN: 1454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.081
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0022	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.2
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Varity_R		0.21
gMVP		0.015
Mutation Taster		=95/5	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-11970557;