8-7949190-A-T

Position:

• chr8-7949190-A-T

Variant summary

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

The NM_001193630.1(ZNF705B):​c.74A>T​(p.Asp25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 7)
• Consequence: ZNF705B NM_001193630.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

Genes affected

ZNF705B (HGNC:32284): (zinc finger protein 705B) 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]

LOC124901865 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF705B	NM_001193630.1	c.74A>T	p.Asp25Val	missense_variant	4/7	ENST00000400120.3	NP_001180559.1
ZNF705B	XM_047421207.1	c.74A>T	p.Asp25Val	missense_variant	4/7		XP_047277163.1
ZNF705B	XM_047421208.1	c.74A>T	p.Asp25Val	missense_variant	2/5		XP_047277164.1
LOC124901865		n.7949190A>T		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF705B	ENST00000400120.3	c.74A>T	p.Asp25Val	missense_variant	4/7	2	NM_001193630.1	ENSP00000382987.3

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 7

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 29, 2023

The c.74A>T (p.D25V) alteration is located in exon 4 (coding exon 2) of the ZNF705B gene. This alteration results from a A to T substitution at nucleotide position 74, causing the aspartic acid (D) at amino acid position 25 to be replaced by a valine (V). 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	0.65
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0017	T
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.65		Loss of disorder (P = 0.0115);
MVP		0.068
ClinPred		0.98	D
GERP RS		0.64
Varity_R		0.72
gMVP		0.055

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: chr8-7806712;