rs62621812

Variant names:

• chr7-127375029-G-A
• rs62621812
• NM_176814.5:c.307C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/20 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
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2642 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176814.5. 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
	ZNF800	NM_176814.5	MANE Select	c.307C>T	p.Pro103Ser	missense	Exon 5 of 6	NP_789784.2
	ZNF800	NM_001438587.1		c.307C>T	p.Pro103Ser	missense	Exon 5 of 6	NP_001425516.1
	ZNF800	NM_001438588.1		c.211C>T	p.Pro71Ser	missense	Exon 4 of 5	NP_001425517.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF800	ENST00000265827.8	TSL:1 MANE Select	c.307C>T	p.Pro103Ser	missense	Exon 5 of 6	ENSP00000265827.3	Q2TB10
	ZNF800	ENST00000393312.5	TSL:5	c.307C>T	p.Pro103Ser	missense	Exon 5 of 6	ENSP00000376988.1	Q2TB10
	ZNF800	ENST00000393313.5	TSL:5	c.307C>T	p.Pro103Ser	missense	Exon 5 of 6	ENSP00000376989.1	Q2TB10

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

GnomAD2 exomes AF: 0.0178 AC: 3892 AN: 218762 AF XY: 0.0176

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 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

African (AFR) AF: 0.00306 AC: 97 AN: 31684

American (AMR) AF: 0.00712 AC: 268 AN: 37618

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 355 AN: 23602

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39328

South Asian (SAS) AF: 0.00361 AC: 286 AN: 79246

European-Finnish (FIN) AF: 0.0457 AC: 2173 AN: 47558

Middle Eastern (MID) AF: 0.00906 AC: 50 AN: 5520

European-Non Finnish (NFE) AF: 0.0227 AC: 24764 AN: 1092398

Other (OTH) AF: 0.0164 AC: 957 AN: 58332

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

African (AFR) AF: 0.00320 AC: 133 AN: 41514

American (AMR) AF: 0.00656 AC: 100 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4820

European-Finnish (FIN) AF: 0.0562 AC: 595 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0247 AC: 1680 AN: 67984

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0211 Hom.: 139

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 v4.9

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
Eigen	Benign	-0.21
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.86	D
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.9
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.078
Sift	Benign	0.32	T
Sift4G	Benign	0.58	T
Polyphen		0.15	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

Other links and lift over

dbSNP: rs62621812; hg19: chr7-127015083;