rs4987042

Positions:

• chr19-51968610-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_021632.4(ZNF350):​c.206T>C​(p.Ile69Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,614,038 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (7 hom.)
• Consequence: ZNF350 NM_021632.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

Genes affected

ZNF350 (HGNC:16656): (zinc finger protein 350) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of transcription repressor complex. [provided by Alliance of Genome Resources, Apr 2022]

ZNF350-AS1 (HGNC:48598): (ZNF350 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005890608).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF350	NM_021632.4	c.206T>C	p.Ile69Thr	missense_variant	4/5	ENST00000243644.9	NP_067645.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF350	ENST00000243644.9	c.206T>C	p.Ile69Thr	missense_variant	4/5	1	NM_021632.4	ENSP00000243644.3

Frequencies

GnomAD3 genomes AF: 0.00266 AC: 404 AN: 152054 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00157 AC: 396 AN: 251446 Hom.: 2 AF XY: 0.00154 AC XY: 209 AN XY: 135900

Gnomad AFR exome AF: 0.00671

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00185 AC: 2707 AN: 1461866 Hom.: 7 Cov.: 32 AF XY: 0.00179 AC XY: 1305 AN XY: 727236

Gnomad4 AFR exome AF: 0.00744

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00202

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00267 AC: 406 AN: 152172 Hom.: 2 Cov.: 32 AF XY: 0.00255 AC XY: 190 AN XY: 74394

Gnomad4 AFR AF: 0.00576

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00214 Hom.: 1

Bravo AF: 0.00323

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.00704 AC: 31

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.00161 AC: 196

Asia WGS AF: 0.00722 AC: 25 AN: 3478

EpiCase AF: 0.00256

EpiControl AF: 0.00273

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.0010
DANN	Benign	0.12
DEOGEN2	Benign	0.036	T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.0046	T;T
M_CAP	Benign	0.00087	T
MetaRNN	Benign	0.0059	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.18	N;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.016
Sift	Benign	1.0	T;.
Sift4G	Benign	0.89	T;T
Polyphen		0.0	B;.
Vest4		0.032
MVP		0.055
MPC		0.25
ClinPred		0.0016	T
GERP RS		-2.9
Varity_R		0.024
gMVP		0.011

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: rs4987042; hg19: chr19-52471863;