rs351779

Variant names:

• chr8-28346747-G-A
• rs351779
• NM_018660.3:c.*1972C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018660.3(ZNF395):​c.*1972C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,134 control chromosomes in the GnomAD database, including 13,308 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (13301 hom., cov: 27)
  • Exomes 𝑓: 0.60 (7 hom.)
• Consequence: ZNF395 NM_018660.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• Publications: 13 publications found

Genes affected

ZNF395 (HGNC:18737): (zinc finger protein 395) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF395	NM_018660.3	c.*1972C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000344423.10	NP_061130.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF395	ENST00000344423.10	c.*1972C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_018660.3	ENSP00000340494.5

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58695 AN: 150978 Hom.: 13312 Cov.: 27

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.392

GnomAD4 exome AF: 0.600 AC: 24 AN: 40 Hom.: 7 Cov.: 0 AF XY: 0.594 AC XY: 19 AN XY: 32

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 15 AN: 24

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.388 AC: 58676 AN: 151094 Hom.: 13301 Cov.: 27 AF XY: 0.383 AC XY: 28243 AN XY: 73710

African (AFR) AF: 0.185 AC: 7621 AN: 41184

American (AMR) AF: 0.306 AC: 4661 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3466

East Asian (EAS) AF: 0.170 AC: 868 AN: 5106

South Asian (SAS) AF: 0.333 AC: 1581 AN: 4750

European-Finnish (FIN) AF: 0.519 AC: 5385 AN: 10380

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.527 AC: 35637 AN: 67678

Other (OTH) AF: 0.386 AC: 813 AN: 2108

Alfa AF: 0.481 Hom.: 35099

Bravo AF: 0.362

Asia WGS AF: 0.240 AC: 836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.63
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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: rs351779; hg19: chr8-28204264;