6-28329527-G-T

Position:

• chr6-28329527-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_030899.5(ZSCAN31):​c.157C>A​(p.Pro53Thr) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN31 NM_030899.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.62

Genes affected

ZSCAN31 (HGNC:14097): (zinc finger and SCAN domain containing 31) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN31	NM_030899.5	c.157C>A	p.Pro53Thr	missense_variant	2/4	ENST00000344279.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN31	ENST00000344279.11	c.157C>A	p.Pro53Thr	missense_variant	2/4	1	NM_030899.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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 02, 2021

The c.157C>A (p.P53T) alteration is located in exon 2 (coding exon 1) of the ZSCAN31 gene. This alteration results from a C to A substitution at nucleotide position 157, causing the proline (P) at amino acid position 53 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	0.76
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;T;T;.;T;T;T;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.86	.;.;.;D;D;D;D;D;D;D
M_CAP	Benign	0.0070	T
MetaRNN	Pathogenic	0.96	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.99	T
MutationAssessor	Pathogenic	4.5	H;H;H;H;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-7.0	D;D;D;D;D;D;D;D;D;D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D;D;D;D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;.;.;.;.;D
Polyphen		0.97	D;D;D;D;.;.;.;.;.;.
Vest4		0.42
MutPred		0.89		Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);Gain of phosphorylation at P53 (P = 0.0207);
MVP		0.45
MPC		0.52
ClinPred		0.99	D
GERP RS		3.0
Varity_R		0.79
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-28297304;