chr1-71078479-C-T

Position:

• chr1-71078479-C-T

Variant summary

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

The NM_203350.3(ZRANB2):​c.196G>A​(p.Ala66Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZRANB2 NM_203350.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

Genes affected

ZRANB2 (HGNC:13058): (zinc finger RANBP2-type containing 2) Enables RNA binding activity. Predicted to be involved in RNA splicing and mRNA processing. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
ZRANB2	NM_203350.3	c.196G>A	p.Ala66Thr	missense_variant	3/10	ENST00000370920.8	NP_976225.1
ZRANB2	NM_005455.5	c.196G>A	p.Ala66Thr	missense_variant	3/11		NP_005446.2
ZRANB2	XM_047434733.1	c.196G>A	p.Ala66Thr	missense_variant	3/10		XP_047290689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB2	ENST00000370920.8	c.196G>A	p.Ala66Thr	missense_variant	3/10	1	NM_203350.3	ENSP00000359958.3
ZRANB2	ENST00000254821.10	c.196G>A	p.Ala66Thr	missense_variant	3/11	1		ENSP00000254821.6
ZRANB2	ENST00000611683.1	c.196G>A	p.Ala66Thr	missense_variant	3/10	2		ENSP00000482026.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.196G>A (p.A66T) alteration is located in exon 3 (coding exon 3) of the ZRANB2 gene. This alteration results from a G to A substitution at nucleotide position 196, causing the alanine (A) at amino acid position 66 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	D;.;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;.;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.9	D;D;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.021	D;D;.
Sift4G	Uncertain	0.017	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.69
MutPred		0.46		Loss of MoRF binding (P = 0.1108);Loss of MoRF binding (P = 0.1108);Loss of MoRF binding (P = 0.1108);
MVP		0.22
MPC		2.5
ClinPred		1.0	D
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.46
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-71544162;