6-28085686-G-A

Variant names:

• chr6-28085686-G-A
• rs150684212
• NM_001376491.1:c.206G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001376491.1(ZNF165):​c.206G>A​(p.Arg69His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,614,084 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00081 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: ZNF165 NM_001376491.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.554
• Publications: 5 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017923683).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

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.206G>A	p.Arg69His	missense	Exon 2 of 4	NP_001363420.1	P49910
	ZNF165	NM_001376492.1		c.206G>A	p.Arg69His	missense	Exon 2 of 4	NP_001363421.1	P49910
	ZNF165	NM_001376493.1		c.206G>A	p.Arg69His	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.206G>A	p.Arg69His	missense	Exon 2 of 4	ENSP00000507525.1	P49910
	ZNF165	ENST00000377325.2	TSL:1	c.206G>A	p.Arg69His	missense	Exon 2 of 4	ENSP00000366542.1	P49910
	ZNF165	ENST00000893308.1		c.206G>A	p.Arg69His	missense	Exon 2 of 4	ENSP00000563367.1

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000741 AC: 186 AN: 251134 AF XY: 0.000781

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000925

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.00126 AC: 1836 AN: 1461746 Hom.: 3 Cov.: 31 AF XY: 0.00126 AC XY: 914 AN XY: 727176

African (AFR) AF: 0.000209 AC: 7 AN: 33478

American (AMR) AF: 0.000827 AC: 37 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86250

European-Finnish (FIN) AF: 0.000112 AC: 6 AN: 53406

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5664

European-Non Finnish (NFE) AF: 0.00154 AC: 1715 AN: 1112004

Other (OTH) AF: 0.000778 AC: 47 AN: 60384

GnomAD4 genome AF: 0.000814 AC: 124 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.000805 AC XY: 60 AN XY: 74492

African (AFR) AF: 0.000337 AC: 14 AN: 41574

American (AMR) AF: 0.000980 AC: 15 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00113 Hom.: 1

Bravo AF: 0.000975

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000749 AC: 91

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00153

EpiControl AF: 0.00107

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	0.18
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	9.4
DANN	Benign	0.91
DEOGEN2	Benign	0.029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		-0.55
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.086
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.94	P
Vest4		0.27
MVP		0.13
MPC		0.50
ClinPred		0.088	T
GERP RS		-3.5
Varity_R		0.075
gMVP		0.10
Mutation Taster		=99/1	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: rs150684212; hg19: chr6-28053464; COSMIC: COSV66102627; COSMIC: COSV66102627;