chr12-8177359-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF705A	NM_001004328.3	c.679C>T	p.Pro227Ser	missense_variant	Exon 6 of 6	ENST00000396570.8	NP_001004328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF705A	ENST00000396570.8	c.679C>T	p.Pro227Ser	missense_variant	Exon 6 of 6	5	NM_001004328.3	ENSP00000379816.4
ZNF705A	ENST00000359286.4	c.679C>T	p.Pro227Ser	missense_variant	Exon 5 of 5	2		ENSP00000352233.4
ZNF705A	ENST00000610508.4	c.679C>T	p.Pro227Ser	missense_variant	Exon 6 of 6	5		ENSP00000481663.1
ZNF705A	ENST00000398526.2	c.271+174C>T		intron_variant	Intron 2 of 2	3		ENSP00000475525.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.679C>T (p.P227S) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a C to T substitution at nucleotide position 679, causing the proline (P) at amino acid position 227 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-7.5	.;D
REVEL	Benign	0.15
Sift	Benign	0.066	.;T
Sift4G	Benign	0.11	T;T
Polyphen		0.69	P;P
Vest4		0.13
MutPred		0.52		Gain of MoRF binding (P = 0.0544);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-8329955;