NM_001376491.1:c.1045T>C

Variant names:

• chr6-28089057-T-C
• rs1382688660
• NM_001376491.1:c.1045T>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.1045T>C​(p.Cys349Arg) 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. 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. C349S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF165 NM_001376491.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• 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, 0.954

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.1045T>C	p.Cys349Arg	missense	Exon 4 of 4	NP_001363420.1	P49910
	ZNF165	NM_001376492.1		c.1045T>C	p.Cys349Arg	missense	Exon 4 of 4	NP_001363421.1	P49910
	ZNF165	NM_001376493.1		c.1045T>C	p.Cys349Arg	missense	Exon 4 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.1045T>C	p.Cys349Arg	missense	Exon 4 of 4	ENSP00000507525.1	P49910
	ZNF165	ENST00000377325.2	TSL:1	c.1045T>C	p.Cys349Arg	missense	Exon 4 of 4	ENSP00000366542.1	P49910
	ZNF165	ENST00000893308.1		c.1045T>C	p.Cys349Arg	missense	Exon 4 of 4	ENSP00000563367.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.070	T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.0027	T
MutationAssessor	Pathogenic	4.3	H
PhyloP100		3.4
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.61
MutPred		0.90		Gain of MoRF binding (P = 0.0086)
MVP		0.80
MPC		0.89
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.90
gMVP		0.26
Mutation Taster		=96/4	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: rs1382688660; hg19: chr6-28056835;