chr6-28085661-C-T

Variant names:

• chr6-28085661-C-T
• rs143050119
• NM_001376491.1:c.181C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001376491.1(ZNF165):​c.181C>T​(p.Pro61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000133 in 1,614,190 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: ZNF165 NM_001376491.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.469
• 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_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023611069).

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.181C>T	p.Pro61Ser	missense	Exon 2 of 4	NP_001363420.1	P49910
	ZNF165	NM_001376492.1		c.181C>T	p.Pro61Ser	missense	Exon 2 of 4	NP_001363421.1	P49910
	ZNF165	NM_001376493.1		c.181C>T	p.Pro61Ser	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.181C>T	p.Pro61Ser	missense	Exon 2 of 4	ENSP00000507525.1	P49910
	ZNF165	ENST00000377325.2	TSL:1	c.181C>T	p.Pro61Ser	missense	Exon 2 of 4	ENSP00000366542.1	P49910
	ZNF165	ENST00000893308.1		c.181C>T	p.Pro61Ser	missense	Exon 2 of 4	ENSP00000563367.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000191 AC: 48 AN: 251318 AF XY: 0.000250

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000130 AC: 190 AN: 1461850 Hom.: 1 Cov.: 31 AF XY: 0.000164 AC XY: 119 AN XY: 727224

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000176 AC: 7 AN: 39700

South Asian (SAS) AF: 0.00152 AC: 131 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112012

Other (OTH) AF: 0.000662 AC: 40 AN: 60396

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74494

African (AFR) AF: 0.000241 AC: 10 AN: 41578

American (AMR) AF: 0.0000653 AC: 1 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000117

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000247 AC: 30

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	0.22
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.8
DANN	Benign	0.18
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.80	N
PhyloP100		-0.47
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.036
Sift	Benign	0.95	T
Sift4G	Benign	0.26	T
Polyphen		0.44	B
Vest4		0.30
MVP		0.24
MPC		0.31
ClinPred		0.047	T
GERP RS		1.7
Varity_R		0.027
gMVP		0.054
Mutation Taster		=98/2	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: rs143050119; hg19: chr6-28053439;