dbSNP rs377006128: SERTAD3:p.Glu86Gln (chr19-40441825-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203344.3(SERTAD3):c.256G>C(p.Glu86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E86K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SERTAD3
NM_203344.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14

Variant links:

Genes affected

SERTAD3 (HGNC:17931): (SERTA domain containing 3) The protein encoded by this gene was identified in a yeast two-hybrid assay employing the second subunit of human replication protein A as bait. It is localized to the nucleus and its expression is significantly higher in cancer cell lines compared to normal cell lines. This protein has also been shown to be a strong transcriptional co-activator. Alternative splicing has been observed at this locus and two variants, both encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

SERTAD3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17027965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERTAD3	NM_203344.3 link	c.256G>C	p.Glu86Gln	missense_variant	Exon 2 of 2	ENST00000322354.4	NP_976219.1	Q9UJW9A0A024R0N2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERTAD3	ENST00000322354.4 link	c.256G>C	p.Glu86Gln	missense_variant	Exon 2 of 2	1	NM_203344.3	ENSP00000325414.2	Q9UJW9
SERTAD3	ENST00000392028.8 link	c.256G>C	p.Glu86Gln	missense_variant	Exon 2 of 2	1		ENSP00000375882.3	Q9UJW9
SERTAD3	ENST00000599706.1 link	c.256G>C	p.Glu86Gln	missense_variant	Exon 2 of 2	2		ENSP00000469245.1	M0QXL4
SERTAD3	ENST00000596456.1 link	c.256G>C	p.Glu86Gln	missense_variant	Exon 3 of 3	3		ENSP00000472999.1	M0R352

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435476

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.023

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

T;T;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.80

.;T;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.1

N;N;.;.

REVEL

Benign

0.074

Sift

Benign

0.13

T;T;.;.

Sift4G

Pathogenic

0.0

D;D;.;.

Polyphen

0.96

P;P;.;.

Vest4

0.27

MutPred

0.17

Loss of phosphorylation at S90 (P = 0.1414);Loss of phosphorylation at S90 (P = 0.1414);Loss of phosphorylation at S90 (P = 0.1414);Loss of phosphorylation at S90 (P = 0.1414);

MVP

0.26

MPC

0.71

ClinPred

0.57

GERP RS

5.3

Varity_R

0.13

gMVP

0.23

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over