chr9-37441810-C-G

Variant names:

• chr9-37441810-C-G
• rs752779286
• NM_014872.3:c.742G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014872.3(ZBTB5):​c.742G>C​(p.Gly248Arg) 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 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZBTB5 NM_014872.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28
• Publications: 0 publications found

Genes affected

ZBTB5 (HGNC:23836): (zinc finger and BTB domain containing 5) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06348142).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014872.3. 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
	ZBTB5	NM_014872.3	MANE Select	c.742G>C	p.Gly248Arg	missense	Exon 2 of 2	NP_055687.1	O15062

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZBTB5	ENST00000307750.5	TSL:1 MANE Select	c.742G>C	p.Gly248Arg	missense	Exon 2 of 2	ENSP00000307604.4	O15062
	ZBTB5	ENST00000860851.1		c.742G>C	p.Gly248Arg	missense	Exon 2 of 2	ENSP00000530910.1
	ZBTB5	ENST00000933754.1		c.742G>C	p.Gly248Arg	missense	Exon 2 of 2	ENSP00000603813.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

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: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.073
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.43	B
Vest4		0.16
MutPred		0.18		Gain of loop (P = 0.024)
MVP		0.043
MPC		0.33
ClinPred		0.23	T
GERP RS		4.7
Varity_R		0.13
gMVP		0.24
Mutation Taster		=95/5	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: rs752779286; hg19: chr9-37441807;