chr6-28085559-G-A

Variant names:

• chr6-28085559-G-A
• NM_001376491.1:c.79G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376491.1(ZNF165):​c.79G>A​(p.Glu27Lys) 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. 13/22 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: ZNF165 NM_001376491.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

ZNF165 (HGNC:12953): (zinc finger protein 165) This gene encodes a member of the Kruppel family of zinc finger proteins. Members of this DNA-binding protein family act as transcriptional regulators. This gene is located within a cluster of zinc finger family members. The encoded protein may play a role in spermatogenesis. [provided by RefSeq, Jul 2008]

ZSCAN16-AS1 (HGNC:48982): (ZSCAN16 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17961106).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376491.1. 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
	ZNF165	NM_001376491.1	MANE Select	c.79G>A	p.Glu27Lys	missense	Exon 2 of 4	NP_001363420.1	P49910
	ZNF165	NM_001376492.1		c.79G>A	p.Glu27Lys	missense	Exon 2 of 4	NP_001363421.1	P49910
	ZNF165	NM_001376493.1		c.79G>A	p.Glu27Lys	missense	Exon 2 of 4	NP_001363422.1	Q53Z40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF165	ENST00000683778.1	MANE Select	c.79G>A	p.Glu27Lys	missense	Exon 2 of 4	ENSP00000507525.1	P49910
	ZNF165	ENST00000377325.2	TSL:1	c.79G>A	p.Glu27Lys	missense	Exon 2 of 4	ENSP00000366542.1	P49910
	ZNF165	ENST00000893308.1		c.79G>A	p.Glu27Lys	missense	Exon 2 of 4	ENSP00000563367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.050
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.11	T
Sift4G	Uncertain	0.010	D
Polyphen		0.63	P
Vest4		0.39
MutPred		0.60		Gain of methylation at E27 (P = 0.0086)
MVP		0.46
MPC		0.68
ClinPred		0.81	D
GERP RS		1.8
Varity_R		0.088
gMVP		0.14
Mutation Taster		=93/7	polymorphism

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

hg19: chr6-28053337;