14-64522570-A-G

Variant names:

• chr14-64522570-A-G
• rs376945184
• NM_001123329.2:c.1066A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001123329.2(ZBTB1):​c.1066A>G​(p.Thr356Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T356P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZBTB1 NM_001123329.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06803164).

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.1066A>G	p.Thr356Ala	missense	Exon 2 of 2	NP_001116801.1	Q9Y2K1-1
	ZBTB1	NM_001438534.1		c.1066A>G	p.Thr356Ala	missense	Exon 5 of 5	NP_001425463.1
	ZBTB1	NM_014950.3		c.1066A>G	p.Thr356Ala	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.1066A>G	p.Thr356Ala	missense	Exon 2 of 2	ENSP00000506911.1	Q9Y2K1-1
	ZBTB1	ENST00000554015.5	TSL:1	c.1066A>G	p.Thr356Ala	missense	Exon 4 of 4	ENSP00000451000.1	Q9Y2K1-1
	ZBTB1	ENST00000358738.3	TSL:1	c.1066A>G	p.Thr356Ala	missense	Exon 2 of 3	ENSP00000351587.3	Q9Y2K1-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
PhyloP100		2.3
Varity_R		0.036
gMVP		0.28
Mutation Taster		=89/11	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs376945184; hg19: chr14-64989288; COSMIC: COSV62439695; COSMIC: COSV62439695;