2-179116713-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_178123.5(SESTD1):​c.1602G>A​(p.Thr534Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,614,096 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

SESTD1
NM_178123.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.853
Variant links:
Genes affected
SESTD1 (HGNC:18379): (SEC14 and spectrin domain containing 1) Enables phosphatidylinositol-3,4-bisphosphate binding activity and phospholipid binding activity. Involved in negative regulation of calcium ion transmembrane transport via high voltage-gated calcium channel. Located in intermediate filament cytoskeleton. Colocalizes with calcium channel complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 2-179116713-C-T is Benign according to our data. Variant chr2-179116713-C-T is described in ClinVar as [Benign]. Clinvar id is 770877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.853 with no splicing effect.
BS2
High AC in GnomAd4 at 267 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SESTD1NM_178123.5 linkc.1602G>A p.Thr534Thr synonymous_variant Exon 15 of 18 ENST00000428443.8 NP_835224.3 Q86VW0B3KTX3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SESTD1ENST00000428443.8 linkc.1602G>A p.Thr534Thr synonymous_variant Exon 15 of 18 1 NM_178123.5 ENSP00000415332.2 Q86VW0
SESTD1ENST00000335289.5 linkn.*319G>A non_coding_transcript_exon_variant Exon 7 of 10 5 ENSP00000334183.5 H7BXT9
SESTD1ENST00000446758.5 linkn.537G>A non_coding_transcript_exon_variant Exon 5 of 8 2 ENSP00000410632.1 H0Y774
SESTD1ENST00000335289.5 linkn.*319G>A 3_prime_UTR_variant Exon 7 of 10 5 ENSP00000334183.5 H7BXT9

Frequencies

GnomAD3 genomes
AF:
0.00175
AC:
267
AN:
152188
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000627
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00334
Gnomad ASJ
AF:
0.00808
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00216
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00197
AC:
495
AN:
251200
Hom.:
1
AF XY:
0.00194
AC XY:
264
AN XY:
135760
show subpopulations
Gnomad AFR exome
AF:
0.000554
Gnomad AMR exome
AF:
0.00208
Gnomad ASJ exome
AF:
0.0106
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.00247
Gnomad OTH exome
AF:
0.00326
GnomAD4 exome
AF:
0.00200
AC:
2918
AN:
1461790
Hom.:
6
Cov.:
31
AF XY:
0.00195
AC XY:
1420
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.00210
Gnomad4 ASJ exome
AF:
0.00991
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.00215
Gnomad4 OTH exome
AF:
0.00222
GnomAD4 genome
AF:
0.00175
AC:
267
AN:
152306
Hom.:
0
Cov.:
32
AF XY:
0.00187
AC XY:
139
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000625
Gnomad4 AMR
AF:
0.00333
Gnomad4 ASJ
AF:
0.00808
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.00216
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00206
Hom.:
1
Bravo
AF:
0.00187
Asia WGS
AF:
0.000578
AC:
2
AN:
3476
EpiCase
AF:
0.00191
EpiControl
AF:
0.00243

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jul 31, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.26
CADD
Benign
5.3
DANN
Benign
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs76833045; hg19: chr2-179981440; COSMIC: COSV58931027; API