12-8175938-C-T

Variant names:

• chr12-8175938-C-T
• rs778398314
• NM_001004328.3:c.314C>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.314C>T​(p.Thr105Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T105K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF705A NM_001004328.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182

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=0.094038755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF705A	NM_001004328.3	c.314C>T	p.Thr105Ile	missense_variant	Exon 5 of 6	ENST00000396570.8	NP_001004328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF705A	ENST00000396570.8	c.314C>T	p.Thr105Ile	missense_variant	Exon 5 of 6	5	NM_001004328.3	ENSP00000379816.4
ZNF705A	ENST00000359286.4	c.314C>T	p.Thr105Ile	missense_variant	Exon 4 of 5	2		ENSP00000352233.4
ZNF705A	ENST00000610508.4	c.314C>T	p.Thr105Ile	missense_variant	Exon 5 of 6	5		ENSP00000481663.1
ZNF705A	ENST00000398526.2	c.80C>T	p.Thr27Ile	missense_variant	Exon 1 of 3	3		ENSP00000475525.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459152 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725888

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0055	.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.51	T;T;.
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	.;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.3	N;.;N
REVEL	Benign	0.031
Sift	Benign	0.34	T;.;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.27	.;B;B
Vest4		0.17, 0.17
MutPred		0.15		Loss of glycosylation at T105 (P = 0.0314);Loss of glycosylation at T105 (P = 0.0314);Loss of glycosylation at T105 (P = 0.0314);
MVP		0.30
MPC		1.7
ClinPred		0.095	T
GERP RS		0.015
Varity_R		0.043
gMVP		0.093

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

LitVar

Other links and lift over

dbSNP: rs778398314; hg19: chr12-8328534;