NM_001039615.3:c.795T>G

Variant names:

• chr8-12113050-T-G
• rs373627730
• NM_001039615.3:c.795T>G

Variant summary

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

The NM_001039615.3(ZNF705D):​c.795T>G​(p.Phe265Leu) variant causes a missense 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 16)
  • Exomes 𝑓: 0.00015 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF705D NM_001039615.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.129
• 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=0.20691669).

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.795T>G	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.795T>G	p.Phe265Leu	missense	Exon 7 of 7	ENSP00000382957.3	P0CH99

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 13 AN: 115878 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000277

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: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000999 AC: 9 AN: 90116 AF XY: 0.000108

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000219

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000153 AC: 197 AN: 1289020 Hom.: 5 Cov.: 29 AF XY: 0.000140 AC XY: 90 AN XY: 641574

⚠️ 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: 32360

American (AMR) AF: 0.00 AC: 0 AN: 34388

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23004

East Asian (EAS) AF: 0.00 AC: 0 AN: 34110

South Asian (SAS) AF: 0.00 AC: 0 AN: 76126

European-Finnish (FIN) AF: 0.000351 AC: 16 AN: 45564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3662

European-Non Finnish (NFE) AF: 0.000177 AC: 175 AN: 986412

Other (OTH) AF: 0.000112 AC: 6 AN: 53394

⚠️ 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: 0.000112 AC: 13 AN: 115878 Hom.: 0 Cov.: 16 AF XY: 0.000126 AC XY: 7 AN XY: 55524

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

African (AFR) AF: 0.0000277 AC: 1 AN: 36116

American (AMR) AF: 0.00 AC: 0 AN: 9206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3148

South Asian (SAS) AF: 0.00 AC: 0 AN: 3060

European-Finnish (FIN) AF: 0.000754 AC: 5 AN: 6634

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

European-Non Finnish (NFE) AF: 0.000133 AC: 7 AN: 52760

Other (OTH) AF: 0.00 AC: 0 AN: 1464

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000564528), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000387 AC: 2

ExAC AF: 0.000112 AC: 9

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	0.87
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.13
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.053
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.34
MutPred		0.74		Gain of ubiquitination at K263 (P = 0.0671)
MVP		0.30
ClinPred		0.87	D
Varity_R		0.23
gMVP		0.015
Mutation Taster		=94/6	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: rs373627730; hg19: chr8-11970559;