chr12-8177404-A-T

Position:

• chr12-8177404-A-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.724A>T​(p.Asn242Tyr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF705A NM_001004328.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -6.63

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=0.07930717).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705A	NM_001004328.3	c.724A>T	p.Asn242Tyr	missense_variant	6/6	ENST00000396570.8	NP_001004328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705A	ENST00000396570.8	c.724A>T	p.Asn242Tyr	missense_variant	6/6	5	NM_001004328.3	ENSP00000379816	P1
ZNF705A	ENST00000359286.4	c.724A>T	p.Asn242Tyr	missense_variant	5/5	2		ENSP00000352233	P1
ZNF705A	ENST00000610508.4	c.724A>T	p.Asn242Tyr	missense_variant	6/6	5		ENSP00000481663	P1
ZNF705A	ENST00000398526.2	c.273+219A>T		intron_variant		3		ENSP00000475525

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 81

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.724A>T (p.N242Y) alteration is located in exon 5 (coding exon 5) of the ZNF705A gene. This alteration results from a A to T substitution at nucleotide position 724, causing the asparagine (N) at amino acid position 242 to be replaced by a tyrosine (Y). 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	Benign	0.33
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.3
DANN	Benign	0.83
DEOGEN2	Benign	0.0039	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Uncertain	0.86	D;.
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.79	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.012
Sift	Benign	0.68	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.27	B;B
Vest4		0.11
MutPred		0.57		Loss of disorder (P = 0.0881);Loss of disorder (P = 0.0881);
MVP		0.20
MPC		1.9
ClinPred		0.095	T
GERP RS		-1.4
Varity_R		0.029
gMVP		0.037

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: chr12-8330000;