chr12-8177359-C-T

Variant names:

• chr12-8177359-C-T
• NM_001004328.3:c.679C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004328.3(ZNF705A):​c.679C>T​(p.Pro227Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF705A NM_001004328.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

ZNF705A (HGNC:32281): (zinc finger protein 705A) 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. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19149679).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004328.3. 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
	ZNF705A	NM_001004328.3	MANE Select	c.679C>T	p.Pro227Ser	missense	Exon 6 of 6	NP_001004328.1	Q6ZN79

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF705A	ENST00000396570.8	TSL:5 MANE Select	c.679C>T	p.Pro227Ser	missense	Exon 6 of 6	ENSP00000379816.4	Q6ZN79
	ZNF705A	ENST00000359286.4	TSL:2	c.679C>T	p.Pro227Ser	missense	Exon 5 of 5	ENSP00000352233.4	Q6ZN79
	ZNF705A	ENST00000610508.4	TSL:5	c.679C>T	p.Pro227Ser	missense	Exon 6 of 6	ENSP00000481663.1	Q6ZN79

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1459670 Hom.: 0 Cov.: 79 AF XY: 0.00 AC XY: 0 AN XY: 726140

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4144

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111814

Other (OTH) AF: 0.00 AC: 0 AN: 60196

GnomAD4 genome Cov.: 32

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	0.85
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.3
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.15
Sift	Benign	0.066	T
Sift4G	Benign	0.11	T
Polyphen		0.69	P
Vest4		0.13
MutPred		0.52		Gain of MoRF binding (P = 0.0544)
MVP		0.37
MPC		1.3
ClinPred		0.61	D
GERP RS		0.43
Varity_R		0.14
gMVP		0.020
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

hg19: chr12-8329955;