Genetic Variant NM_003943.5:c.130C>T (chr4-76306899-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003943.5(STBD1):c.130C>T(p.Leu44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

STBD1
NM_003943.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00600

Publications

0 publications found

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]

STBD1 links:

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]

FAM47E-STBD1 links:

ENSG00000287401 (HGNC:):

ENSG00000287401 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06321329).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003943.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STBD1	NM_003943.5	MANE Select	c.130C>T	p.Leu44Phe	missense	Exon 1 of 2	NP_003934.1	O95210
	FAM47E-STBD1	NM_001242939.2		c.1027-2245C>T		intron	N/A	NP_001229868.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
STBD1	ENST00000237642.7	TSL:1 MANE Select	c.130C>T	p.Leu44Phe	missense	Exon 1 of 2	ENSP00000237642.6	O95210
FAM47E-STBD1	ENST00000515604.5	TSL:2	c.1027-2245C>T		intron	N/A	ENSP00000422067.1
FAM47E-STBD1	ENST00000514140.1	TSL:2	c.547-2245C>T		intron	N/A	ENSP00000423044.2	D6RA91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726442

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25970

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5518

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111494

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.9

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.34

M_CAP

Benign

0.0034

MetaRNN

Benign

0.063

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.0060

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.47

REVEL

Benign

0.090

Sift

Benign

0.091

Sift4G

Benign

0.11

Polyphen

0.70

Vest4

0.016

MutPred

0.10

Gain of methylation at K40 (P = 0.15)

MVP

0.15

MPC

0.16

ClinPred

0.21

GERP RS

0.52

PromoterAI

0.0013

Neutral

(source)

Varity_R

0.048

gMVP

0.062

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over