6-28089183-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376491.1(ZNF165):​c.1171C>G​(p.Arg391Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R391W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZNF165 NM_001376491.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1402337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF165	NM_001376491.1	c.1171C>G	p.Arg391Gly	missense_variant	Exon 4 of 4	ENST00000683778.1	NP_001363420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF165	ENST00000683778.1	c.1171C>G	p.Arg391Gly	missense_variant	Exon 4 of 4		NM_001376491.1	ENSP00000507525.1
ZNF165	ENST00000377325.2	c.1171C>G	p.Arg391Gly	missense_variant	Exon 4 of 4	1		ENSP00000366542.1
ZSCAN16-AS1	ENST00000660873.1	n.78-28695G>C		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251408 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.0050	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.046
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.010	B
Vest4		0.18
MutPred		0.62		Loss of MoRF binding (P = 0.078);
MVP		0.23
MPC		0.25
ClinPred		0.92	D
GERP RS		3.0
Varity_R		0.36
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs150379905; hg19: chr6-28056961;