NM_003943.5:c.52C>A

Variant summary

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

The NM_003943.5(STBD1):​c.52C>A​(p.Leu18Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,612,430 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

STBD1
NM_003943.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27
Variant links:
Genes affected
STBD1 (HGNC:24854): (starch binding domain 1) Enables enzyme binding activity and glycogen binding activity. Involved in glycophagy and intracellular transport. Located in T-tubule; endoplasmic reticulum; and perinuclear region of cytoplasm. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
FAM47E-STBD1 (HGNC:44667): (FAM47E-STBD1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring FAM47E (family with sequence similarity 47, member E) and STBD1 (starch binding domain 1) genes on chromosome 4. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Jul 2011]

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=0.05529338).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STBD1NM_003943.5 linkc.52C>A p.Leu18Ile missense_variant Exon 1 of 2 ENST00000237642.7 NP_003934.1 O95210
FAM47E-STBD1NM_001242939.2 linkc.1027-2323C>A intron_variant Intron 6 of 6 NP_001229868.1 Q6ZV65-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
STBD1ENST00000237642.7 linkc.52C>A p.Leu18Ile missense_variant Exon 1 of 2 1 NM_003943.5 ENSP00000237642.6 O95210
FAM47E-STBD1ENST00000515604.5 linkc.1027-2323C>A intron_variant Intron 6 of 6 2 ENSP00000422067.1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000566
AC:
14
AN:
247204
Hom.:
0
AF XY:
0.0000671
AC XY:
9
AN XY:
134160
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00112
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000288
AC:
42
AN:
1460346
Hom.:
0
Cov.:
31
AF XY:
0.0000399
AC XY:
29
AN XY:
726524
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00100
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.0000830
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000135
Hom.:
0
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.52C>A (p.L18I) alteration is located in exon 1 (coding exon 1) of the STBD1 gene. This alteration results from a C to A substitution at nucleotide position 52, causing the leucine (L) at amino acid position 18 to be replaced by an isoleucine (I). 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
0.097
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.019
T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.47
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.055
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.48
N
REVEL
Benign
0.034
Sift
Benign
0.061
T
Sift4G
Benign
0.55
T
Polyphen
0.73
P
Vest4
0.20
MVP
0.18
MPC
0.11
ClinPred
0.14
T
GERP RS
3.9
Varity_R
0.060
gMVP
0.17

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.

Other links and lift over

dbSNP: rs200284020; hg19: chr4-77227974; API