chr4-76306813-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003943.5(STBD1):​c.44C>T​(p.Ala15Val) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,612,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

STBD1
NM_003943.5 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38148797).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
STBD1NM_003943.5 linkc.44C>T p.Ala15Val missense_variant Exon 1 of 2 ENST00000237642.7 NP_003934.1 O95210
FAM47E-STBD1NM_001242939.2 linkc.1027-2331C>T 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.44C>T p.Ala15Val missense_variant Exon 1 of 2 1 NM_003943.5 ENSP00000237642.6 O95210
FAM47E-STBD1ENST00000515604.5 linkc.1027-2331C>T intron_variant Intron 6 of 6 2 ENSP00000422067.1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000162
AC:
4
AN:
246826
Hom.:
0
AF XY:
0.00000746
AC XY:
1
AN XY:
134090
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000359
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000123
AC:
180
AN:
1460344
Hom.:
0
Cov.:
31
AF XY:
0.000118
AC XY:
86
AN XY:
726498
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00
Gnomad4 NFE exome
AF:
0.000156
Gnomad4 OTH exome
AF:
0.0000995
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152098
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.44C>T (p.A15V) alteration is located in exon 1 (coding exon 1) of the STBD1 gene. This alteration results from a C to T substitution at nucleotide position 44, causing the alanine (A) at amino acid position 15 to be replaced by a valine (V). 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
Uncertain
0.36
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.023
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.68
T
M_CAP
Benign
0.045
D
MetaRNN
Benign
0.38
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.23
Sift
Benign
0.079
T
Sift4G
Benign
0.48
T
Polyphen
1.0
D
Vest4
0.47
MVP
0.43
MPC
0.11
ClinPred
0.96
D
GERP RS
4.7
Varity_R
0.10
gMVP
0.48

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: rs759427326; hg19: chr4-77227966; API