rs62621812

chr7-127375029-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_176814.5(ZNF800):c.307C>T(p.Pro103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,567,422 control chromosomes in the GnomAD database, including 400 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (47 hom., cov: 32)
  • Exomes 𝑓: 0.020 (353 hom.)
• Consequence: ZNF800 NM_176814.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

Genes affected

ZNF800 (HGNC:27267): (zinc finger protein 800) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023738742).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0174 (2642/152136) while in subpopulation NFE AF= 0.0247 (1680/67984). AF 95% confidence interval is 0.0237. There are 47 homozygotes in gnomad4. There are 1393 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2644 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF800	NM_176814.5	c.307C>T	p.Pro103Ser	missense_variant	5/6	ENST00000265827.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF800	ENST00000265827.8	c.307C>T	p.Pro103Ser	missense_variant	5/6	1	NM_176814.5	P1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2644 AN: 152018 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.00321

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.00656

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0562

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0247

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0178 AC: 3892 AN: 218762 Hom.: 63 AF XY: 0.0176 AC XY: 2090 AN XY: 118492

Gnomad AFR exome AF: 0.00325

Gnomad AMR exome AF: 0.00685

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.0000581

Gnomad SAS exome AF: 0.00382

Gnomad FIN exome AF: 0.0509

Gnomad NFE exome AF: 0.0241

Gnomad OTH exome AF: 0.0201

GnomAD4 exome AF: 0.0205 AC: 28951 AN: 1415286 Hom.: 353 Cov.: 33 AF XY: 0.0202 AC XY: 14192 AN XY: 701530

Gnomad4 AFR exome AF: 0.00306

Gnomad4 AMR exome AF: 0.00712

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00361

Gnomad4 FIN exome AF: 0.0457

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0174 AC: 2642 AN: 152136 Hom.: 47 Cov.: 32 AF XY: 0.0187 AC XY: 1393 AN XY: 74386

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.00656

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0562

Gnomad4 NFE AF: 0.0247

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0214 Hom.: 69

Bravo AF: 0.0132

TwinsUK AF: 0.0221 AC: 82

ALSPAC AF: 0.0210 AC: 81

ESP6500AA AF: 0.00341 AC: 15

ESP6500EA AF: 0.0220 AC: 189

ExAC AF: 0.0178 AC: 2163

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	21
Dann	Benign	0.80
DEOGEN2	Benign	0.0047	T;T;T;T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.88	D
MetaRNN	Benign	0.0024	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N;.;.;.
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.24	N;N;N;.;N;N
REVEL	Benign	0.078
Sift	Benign	0.32	T;T;T;.;T;T
Sift4G	Benign	0.58	T;T;T;T;T;T
Polyphen		0.15	B;B;B;.;.;.
Vest4		0.16
MPC		0.26
ClinPred		0.0062	T
GERP RS		4.6
Varity_R		0.042
gMVP		0.47

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: rs62621812; hg19: chr7-127015083;