6-28089183-C-T

Variant names:

• chr6-28089183-C-T
• rs150379905
• NM_001376491.1:c.1171C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001376491.1(ZNF165):​c.1171C>T​(p.Arg391Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,613,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: ZNF165 NM_001376491.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.574
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.009299517).

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.1171C>T	p.Arg391Trp	missense	Exon 4 of 4	NP_001363420.1	P49910
	ZNF165	NM_001376492.1		c.1171C>T	p.Arg391Trp	missense	Exon 4 of 4	NP_001363421.1	P49910
	ZNF165	NM_001376493.1		c.1171C>T	p.Arg391Trp	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.1171C>T	p.Arg391Trp	missense	Exon 4 of 4	ENSP00000507525.1	P49910
	ZNF165	ENST00000377325.2	TSL:1	c.1171C>T	p.Arg391Trp	missense	Exon 4 of 4	ENSP00000366542.1	P49910
	ZNF165	ENST00000893308.1		c.1171C>T	p.Arg391Trp	missense	Exon 4 of 4	ENSP00000563367.1

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152116 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000406 AC: 102 AN: 251408 AF XY: 0.000397

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00813

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000791

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000205 AC: 299 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 166 AN XY: 727236

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00719 AC: 188 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000683 AC: 76 AN: 1112000

Other (OTH) AF: 0.000480 AC: 29 AN: 60394

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152116 Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74298

African (AFR) AF: 0.0000241 AC: 1 AN: 41412

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00663 AC: 23 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000391 Hom.: 0

Bravo AF: 0.000242

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000222 AC: 27

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.26
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.036
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.0093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.57
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.081
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.73	P
Vest4		0.21
MVP		0.35
MPC		0.45
ClinPred		0.10	T
GERP RS		3.0
Varity_R		0.27
gMVP		0.18
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: rs150379905; hg19: chr6-28056961; COSMIC: COSV66102336; COSMIC: COSV66102336;