1-40462880-G-A

Position:

• chr1-40462880-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_023070.3(ZFP69B):​c.896G>A​(p.Arg299Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 1,614,116 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (10 hom.)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.25

Genes affected

ZFP69B (HGNC:28053): (ZFP69 zinc finger protein B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in Golgi organization. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007547885).
• BP6: Variant 1-40462880-G-A is Benign according to our data. Variant chr1-40462880-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 773395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.896G>A	p.Arg299Lys	missense_variant	5/5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.896G>A	p.Arg299Lys	missense_variant	6/6		NP_001356494.1
ZFP69B	XM_005271136.2	c.899G>A	p.Arg300Lys	missense_variant	6/6		XP_005271193.1
ZFP69B	XM_017002147.2	c.899G>A	p.Arg300Lys	missense_variant	6/6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5	c.896G>A	p.Arg299Lys	missense_variant	5/5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.*414G>A		3_prime_UTR_variant	5/5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.896G>A	p.Arg299Lys	missense_variant	6/6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.1548G>A		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.00216 AC: 328 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00364

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00233 AC: 585 AN: 250730 Hom.: 2 AF XY: 0.00251 AC XY: 340 AN XY: 135612

Gnomad AFR exome AF: 0.000867

Gnomad AMR exome AF: 0.00200

Gnomad ASJ exome AF: 0.00666

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000981

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00344

Gnomad OTH exome AF: 0.00229

GnomAD4 exome AF: 0.00335 AC: 4891 AN: 1461806 Hom.: 10 Cov.: 32 AF XY: 0.00336 AC XY: 2441 AN XY: 727192

Gnomad4 AFR exome AF: 0.000597

Gnomad4 AMR exome AF: 0.00203

Gnomad4 ASJ exome AF: 0.00593

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000928

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00387

Gnomad4 OTH exome AF: 0.00336

GnomAD4 genome AF: 0.00215 AC: 328 AN: 152310 Hom.: 0 Cov.: 32 AF XY: 0.00191 AC XY: 142 AN XY: 74476

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00365

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00322 Hom.: 5

Bravo AF: 0.00241

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00407 AC: 35

ExAC AF: 0.00242 AC: 294

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00398

EpiControl AF: 0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0082	T;T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.24	.;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0075	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N;.
REVEL	Benign	0.16
Sift	Benign	0.10	T;.
Sift4G	Benign	0.22	T;T
Polyphen		0.99	D;D
Vest4		0.21
MVP		0.17
MPC		0.43
ClinPred		0.030	T
GERP RS		3.1
Varity_R		0.31
gMVP		0.11

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: rs143880922; hg19: chr1-40928552;