chr16-71867971-C-T

Variant names:

• chr16-71867971-C-T
• rs754538711
• NM_001201552.2:c.107G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001201552.2(ZNF821):​c.107G>A​(p.Gly36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,383,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: ZNF821 NM_001201552.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13
• Publications: 0 publications found

Genes affected

ZNF821 (HGNC:28043): (zinc finger protein 821) This gene encodes a protein with two C2H2 zinc finger motifs and a score-and-three (23)-amino acid peptide repeat (STPR) domain. The STPR domain of the encoded protein binds to double stranded DNA and may also contain a nuclear localization signal, suggesting that this protein interacts with chromosomal DNA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

ATXN1L (HGNC:33279): (ataxin 1 like) Predicted to enable DNA binding activity and RNA binding activity. Predicted to be involved in several processes, including learning or memory; regulation of transcription, DNA-templated; and social behavior. Predicted to act upstream of or within several processes, including lung alveolus development; negative regulation of transcription by RNA polymerase II; and positive regulation of hematopoietic stem cell proliferation. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11472812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201552.2. 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
	ZNF821	NM_001201552.2	MANE Select	c.107G>A	p.Gly36Glu	missense	Exon 4 of 8	NP_001188481.1	O75541-1
	ZNF821	NM_001201553.1		c.107G>A	p.Gly36Glu	missense	Exon 3 of 7	NP_001188482.1	O75541-1
	ZNF821	NM_001376297.1		c.107G>A	p.Gly36Glu	missense	Exon 4 of 8	NP_001363226.1	O75541-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF821	ENST00000425432.6	TSL:5 MANE Select	c.107G>A	p.Gly36Glu	missense	Exon 4 of 8	ENSP00000398089.1	O75541-1
	ZNF821	ENST00000313565.10	TSL:1	c.41-2923G>A		intron	N/A	ENSP00000313822.6	A0A0C4DH12
	ZNF821	ENST00000446827.6	TSL:1	c.41-2923G>A		intron	N/A	ENSP00000405908.2	A0A0C4DH12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000595 AC: 8 AN: 134474 AF XY: 0.0000819

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000666

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000867 AC: 12 AN: 1383742 Hom.: 0 Cov.: 30 AF XY: 0.0000132 AC XY: 9 AN XY: 682812

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.000252 AC: 9 AN: 35732

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078834

Other (OTH) AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000588 AC: 1

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	0.10
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.077
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.1
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Vest4		0.42
MutPred		0.28		Gain of solvent accessibility (P = 0.0456)
MVP		0.13
MPC		2.2
ClinPred		0.20	T
GERP RS		6.0
Varity_R		0.15
gMVP		0.10
Mutation Taster		=72/28	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: rs754538711; hg19: chr16-71901874;