9-122911158-C-G

Variant names:

• chr9-122911158-C-G
• rs371830027
• NM_006626.6:c.915G>C

Variant summary

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

The NM_006626.6(ZBTB6):​c.915G>C​(p.Arg305Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZBTB6 NM_006626.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• Publications: 0 publications found

Genes affected

ZBTB6 (HGNC:16764): (zinc finger and BTB domain containing 6) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in mitochondrion and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1715841).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006626.6. 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
	ZBTB6	NM_006626.6	MANE Select	c.915G>C	p.Arg305Ser	missense	Exon 2 of 2	NP_006617.1	Q15916

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB6	ENST00000373659.4	TSL:1 MANE Select	c.915G>C	p.Arg305Ser	missense	Exon 2 of 2	ENSP00000362763.3	Q15916
	ZBTB6	ENST00000899189.1		c.915G>C	p.Arg305Ser	missense	Exon 2 of 2	ENSP00000569248.1
	ZBTB6	ENST00000899190.1		c.915G>C	p.Arg305Ser	missense	Exon 3 of 3	ENSP00000569249.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 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: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.019
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.92	L
PhyloP100		1.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.46	P
Vest4		0.21
MutPred		0.51		Gain of loop (P = 0.1069)
MVP		0.56
MPC		0.73
ClinPred		0.64	D
GERP RS		4.0
Varity_R		0.45
gMVP		0.63
Mutation Taster		=81/19	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

Other links and lift over

dbSNP: rs371830027; hg19: chr9-125673437;