chr6-28085770-T-C

Variant names:

• chr6-28085770-T-C
• rs751020046
• NM_001376491.1:c.290T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001376491.1(ZNF165):​c.290T>C​(p.Phe97Ser) 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 pathogenic 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: 2.63
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.959

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.290T>C	p.Phe97Ser	missense	Exon 2 of 4	NP_001363420.1	P49910
	ZNF165	NM_001376492.1		c.290T>C	p.Phe97Ser	missense	Exon 2 of 4	NP_001363421.1	P49910
	ZNF165	NM_001376493.1		c.290T>C	p.Phe97Ser	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.290T>C	p.Phe97Ser	missense	Exon 2 of 4	ENSP00000507525.1	P49910
	ZNF165	ENST00000377325.2	TSL:1	c.290T>C	p.Phe97Ser	missense	Exon 2 of 4	ENSP00000366542.1	P49910
	ZNF165	ENST00000893308.1		c.290T>C	p.Phe97Ser	missense	Exon 2 of 4	ENSP00000563367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-6.9	D
REVEL	Benign	0.27
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	D
Vest4		0.79
MutPred		0.86		Loss of stability (P = 0.0824)
MVP		0.60
MPC		0.89
ClinPred		0.95	D
GERP RS		3.1
Varity_R		0.63
gMVP		0.48
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

dbSNP: rs751020046; hg19: chr6-28053548;