chr19-51965015-C-T

Variant names:

• chr19-51965015-C-T
• rs150255847
• NM_021632.4:c.1438G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021632.4(ZNF350):​c.1438G>A​(p.Ala480Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,614,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: ZNF350 NM_021632.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.227
• Publications: 2 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.034777552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021632.4. 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
	ZNF350	NM_021632.4	MANE Select	c.1438G>A	p.Ala480Thr	missense	Exon 5 of 5	NP_067645.3
	ZNF350-AS1	NR_103847.1		n.103-11376C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF350	ENST00000243644.9	TSL:1 MANE Select	c.1438G>A	p.Ala480Thr	missense	Exon 5 of 5	ENSP00000243644.3	Q9GZX5
	ZNF350-AS1	ENST00000595010.5	TSL:1	n.125-11376C>T		intron	N/A
	ZNF350	ENST00000853589.1		c.1507G>A	p.Ala503Thr	missense	Exon 6 of 6	ENSP00000523648.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251174 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000255

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000170 AC: 249 AN: 1461862 Hom.: 1 Cov.: 33 AF XY: 0.000154 AC XY: 112 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000187 AC: 10 AN: 53408

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

European-Non Finnish (NFE) AF: 0.000199 AC: 221 AN: 1112002

Other (OTH) AF: 0.000232 AC: 14 AN: 60394

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74340

African (AFR) AF: 0.0000483 AC: 2 AN: 41428

American (AMR) AF: 0.0000655 AC: 1 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000192 AC: 1 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000222 Hom.: 0

Bravo AF: 0.000121

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000247 AC: 30

EpiCase AF: 0.000109

EpiControl AF: 0.000296

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	0.091
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.4
DANN	Benign	0.96
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.083	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.23
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.11
Sift	Benign	0.47	T
Sift4G	Benign	0.23	T
Polyphen		0.17	B
Vest4		0.094
MVP		0.16
MPC		0.19
ClinPred		0.029	T
GERP RS		-2.0
Varity_R		0.034
gMVP		0.070
Mutation Taster		=100/0	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: rs150255847; hg19: chr19-52468268; COSMIC: COSV54709152; COSMIC: COSV54709152;