dbSNP rs369166936: ZSCAN5A:p.Ser296Cys (chr19-56222180-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001322064.3(ZSCAN5A):c.886A>T(p.Ser296Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000812 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S296G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ZSCAN5A
NM_001322064.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.30

Variant links:

Genes affected

ZSCAN5A (HGNC:23710): (zinc finger and SCAN domain containing 5A) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007597387).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN5A	NM_001322064.3 link	c.886A>T	p.Ser296Cys	missense_variant	Exon 6 of 6	ENST00000683990.1	NP_001308993.1	Q9BUG6-1A0A024R4S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN5A	ENST00000683990.1 link	c.886A>T	p.Ser296Cys	missense_variant	Exon 6 of 6		NM_001322064.3	ENSP00000507065.1		Q9BUG6-1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251462

Hom.:

AF XY:

0.0000883

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461790

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000414

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000614

Hom.:

ExAC

AF:

0.000140

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.022

DANN

Benign

0.40

DEOGEN2

Benign

0.016

T;.;T;T;T

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.33

.;T;T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0076

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.20

N;.;N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.0

N;.;.;.;.

REVEL

Benign

0.024

Sift

Benign

0.094

T;.;.;.;.

Sift4G

Benign

0.061

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.051

MutPred

0.25

Loss of phosphorylation at S296 (P = 0.0091);.;Loss of phosphorylation at S296 (P = 0.0091);.;.;

MVP

0.055

MPC

0.061

ClinPred

0.0085

GERP RS

-4.1

Varity_R

0.050

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over