rs954397858

Variant names:

• chr7-64213213-C-G
• rs954397858
• NM_001159524.1:c.161C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-64213213-C-G
• chr7-64213213-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001159524.1(ZNF735):​c.161C>G​(p.Ser54Cys) 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. 9/13 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. S54F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF735 NM_001159524.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 0 publications found

Genes affected

ZNF735 (HGNC:32466): (zinc finger protein 735) This gene encodes a kruppel-associated box-containing zinc finger protein (KRAB-ZFP). The encoded protein contains an N-terminal kruppel-associated box (KRAB) domain and nine C-terminal C2H2-type zinc finger domains. The KRAB-ZFPs represent the largest family of mammalian transcriptional repressors, which function through the recruitment of the nuclear co-factor KRAB-Associated Protein 1 (KAP1), to engage histone modifiers and induce heterochromatin formation. [provided by RefSeq, Jul 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2678796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159524.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF735	NM_001159524.1	MANE Select	c.161C>G	p.Ser54Cys	missense	Exon 2 of 4	NP_001152996.1	P0CB33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF735	ENST00000429565.5	TSL:5 MANE Select	c.161C>G	p.Ser54Cys	missense	Exon 2 of 4	ENSP00000485547.1	P0CB33

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.086	T
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.27	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-0.26
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.28
MVP		0.014
GERP RS		0.11
Varity_R		0.076
gMVP		0.049

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

Other links and lift over

dbSNP: rs954397858; hg19: chr7-63673591;