NM_001123329.2:c.95A>G

Variant names:

• chr14-64521599-A-G
• rs375361085
• NM_001123329.2:c.95A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001123329.2(ZBTB1):​c.95A>G​(p.Asp32Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: ZBTB1 NM_001123329.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 1 publications found

Genes affected

ZBTB1 (HGNC:20259): (zinc finger and BTB domain containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity; protein heterodimerization activity; and protein homodimerization activity. Involved in several processes, including cellular response to UV; nucleobase-containing compound biosynthetic process; and protein homooligomerization. Located in centrosome; nuclear body; and nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

HSPA2-AS1 (HGNC:55433): (HSPA2 and ZBTB1 antisense RNA 1)

ACMG classification

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

• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001123329.2. 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
	ZBTB1	NM_001123329.2	MANE Select	c.95A>G	p.Asp32Gly	missense	Exon 2 of 2	NP_001116801.1	Q9Y2K1-1
	ZBTB1	NM_001438534.1		c.95A>G	p.Asp32Gly	missense	Exon 5 of 5	NP_001425463.1
	ZBTB1	NM_014950.3		c.95A>G	p.Asp32Gly	missense	Exon 2 of 3	NP_055765.2	Q9Y2K1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB1	ENST00000683701.1	MANE Select	c.95A>G	p.Asp32Gly	missense	Exon 2 of 2	ENSP00000506911.1	Q9Y2K1-1
	ZBTB1	ENST00000554015.5	TSL:1	c.95A>G	p.Asp32Gly	missense	Exon 4 of 4	ENSP00000451000.1	Q9Y2K1-1
	ZBTB1	ENST00000358738.3	TSL:1	c.95A>G	p.Asp32Gly	missense	Exon 2 of 3	ENSP00000351587.3	Q9Y2K1-2

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251440 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1461882 Hom.: 0 Cov.: 34 AF XY: 0.0000303 AC XY: 22 AN XY: 727240

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.0000477 AC: 53 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152232 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68032

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

Alfa AF: 0.0000383 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.72	N
PhyloP100		9.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.44
Sift	Benign	0.37	T
Sift4G	Benign	0.44	T
Polyphen		1.0	D
Vest4		0.71
MVP		0.66
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.44
gMVP		0.77
Mutation Taster		=14/86	disease causing

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: rs375361085; hg19: chr14-64988317; COSMIC: COSV100704097;