chr8-12112973-T-A

Position:

• chr8-12112973-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039615.3(ZNF705D):​c.718T>A​(p.Ser240Thr) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 11)
• Consequence: ZNF705D NM_001039615.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.64

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

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=0.07999557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705D	NM_001039615.3	c.718T>A	p.Ser240Thr	missense_variant	7/7	ENST00000400085.8	NP_001034704.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705D	ENST00000400085.8	c.718T>A	p.Ser240Thr	missense_variant	7/7	5	NM_001039615.3	ENSP00000382957	P1

Frequencies

GnomAD3 genomes Cov.: 11

GnomAD4 exome Cov.: 22

GnomAD4 genome Cov.: 11

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

Jun 01, 2022

The c.718T>A (p.S240T) alteration is located in exon 7 (coding exon 5) of the ZNF705D gene. This alteration results from a T to A substitution at nucleotide position 718, causing the serine (S) at amino acid position 240 to be replaced by a threonine (T). 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	0.25
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.5
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T;T
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.47	.;T
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.016
Sift	Benign	0.26	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.63	P;P
Vest4		0.13
MutPred		0.39		Loss of MoRF binding (P = 0.1271);Loss of MoRF binding (P = 0.1271);
MVP		0.048
ClinPred		0.15	T
GERP RS		0.74
Varity_R		0.044
gMVP		0.0064

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: chr8-11970482;