6-28089157-C-T

Position:

• chr6-28089157-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376491.1(ZNF165):​c.1145C>T​(p.Ala382Val) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF165 NM_001376491.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.00

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060946494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF165	NM_001376491.1	c.1145C>T	p.Ala382Val	missense_variant	4/4	ENST00000683778.1	NP_001363420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF165	ENST00000683778.1	c.1145C>T	p.Ala382Val	missense_variant	4/4		NM_001376491.1	ENSP00000507525.1
ZNF165	ENST00000377325.2	c.1145C>T	p.Ala382Val	missense_variant	4/4	1		ENSP00000366542.1
ZSCAN16-AS1	ENST00000660873.1	n.78-28669G>A		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Sep 08, 2024

The c.1145C>T (p.A382V) alteration is located in exon 4 (coding exon 3) of the ZNF165 gene. This alteration results from a C to T substitution at nucleotide position 1145, causing the alanine (A) at amino acid position 382 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	Benign	0.26
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.00070	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.59	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.040
Sift	Benign	0.096	T
Sift4G	Uncertain	0.026	D
Polyphen		0.13	B
Vest4		0.067
MutPred		0.34		Loss of ubiquitination at K379 (P = 0.0546);
MVP		0.15
MPC		0.19
ClinPred		0.095	T
GERP RS		-2.5
Varity_R		0.033
gMVP		0.027

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: chr6-28056935;