rs139076803

Variant names:

• chr1-32600174-C-A
• rs139076803
• NM_001040441.3:c.1081C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-32600174-C-A
• chr1-32600174-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040441.3(ZBTB8A):​c.1081C>A​(p.Arg361Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R361C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZBTB8A NM_001040441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

Genes affected

ZBTB8A (HGNC:24172): (zinc finger and BTB domain containing 8A) Predicted to enable RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZBTB8OS (HGNC:24094): (zinc finger and BTB domain containing 8 opposite strand) Predicted to enable metal ion binding activity. Involved in tRNA splicing, via endonucleolytic cleavage and ligation. Part of tRNA-splicing ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000254553 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZBTB8A	NM_001040441.3	c.1081C>A	p.Arg361Ser	missense_variant	Exon 5 of 5	ENST00000373510.9	NP_001035531.2
ZBTB8A	NM_001291496.2	c.994-94C>A		intron_variant	Intron 4 of 4		NP_001278425.1
ZBTB8A	NR_111980.2	n.399-94C>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZBTB8A	ENST00000373510.9	c.1081C>A	p.Arg361Ser	missense_variant	Exon 5 of 5	1	NM_001040441.3	ENSP00000362609.3
ENSG00000254553	ENST00000480336.1	n.*1200C>A		non_coding_transcript_exon_variant	Exon 10 of 10	2		ENSP00000455300.1
ENSG00000254553	ENST00000480336.1	n.*1200C>A		3_prime_UTR_variant	Exon 10 of 10	2		ENSP00000455300.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-1.1	T
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Vest4		0.80
MutPred		0.58		Loss of phosphorylation at T359 (P = 0.108);
MVP		0.45
MPC		1.2
ClinPred		0.99	D
GERP RS		5.4
gMVP		0.69

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: rs139076803; hg19: chr1-33065775;