19-40422931-C-T

Variant summary

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

The NM_013376.4(SERTAD1):​c.616G>A​(p.Glu206Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SERTAD1
NM_013376.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.550
Variant links:
Genes affected
SERTAD1 (HGNC:17932): (SERTA domain containing 1) Predicted to be involved in epigenetic maintenance of chromatin in transcription-competent conformation. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.060998082).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SERTAD1NM_013376.4 linkc.616G>A p.Glu206Lys missense_variant Exon 2 of 2 ENST00000357949.5 NP_037508.2 Q9UHV2Q53GC0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SERTAD1ENST00000357949.5 linkc.616G>A p.Glu206Lys missense_variant Exon 2 of 2 1 NM_013376.4 ENSP00000350633.4 Q9UHV2

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
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.616G>A (p.E206K) alteration is located in exon 2 (coding exon 1) of the SERTAD1 gene. This alteration results from a G to A substitution at nucleotide position 616, causing the glutamic acid (E) at amino acid position 206 to be replaced by a lysine (K). 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
Benign
0.088
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.061
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.83
N
REVEL
Benign
0.077
Sift
Benign
0.51
T
Sift4G
Uncertain
0.044
D
Polyphen
0.0030
B
Vest4
0.11
MutPred
0.21
Gain of ubiquitination at E206 (P = 0.0018);
MVP
0.68
MPC
0.35
ClinPred
0.10
T
GERP RS
4.2
Varity_R
0.078
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.

Other links and lift over

hg19: chr19-40928838; COSMIC: COSV63596279; COSMIC: COSV63596279; API