6-28329608-G-A

Position:

• chr6-28329608-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_030899.5(ZSCAN31):​c.76C>T​(p.His26Tyr) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZSCAN31 NM_030899.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.68

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_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035362273).
• BP6: Variant 6-28329608-G-A is Benign according to our data. Variant chr6-28329608-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2493158.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN31	NM_030899.5	c.76C>T	p.His26Tyr	missense_variant	2/4	ENST00000344279.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN31	ENST00000344279.11	c.76C>T	p.His26Tyr	missense_variant	2/4	1	NM_030899.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.0020
DANN	Benign	0.23
DEOGEN2	Benign	0.0023	T;T;T;T;.;T;T;T;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0017	N
LIST_S2	Benign	0.015	.;.;.;T;T;T;T;T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.035	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-1.1	N;N;N;N;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.68	N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.023
Sift	Benign	0.44	T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;.;.;.;.;T
Polyphen		0.0	B;B;B;B;.;.;.;.;.;.
Vest4		0.093
MutPred		0.33		Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);Gain of phosphorylation at H26 (P = 0.0665);
MVP		0.030
MPC		0.11
ClinPred		0.034	T
GERP RS		-8.8
Varity_R		0.025
gMVP		0.18

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: chr6-28297385;