4-76306899-C-T

Variant names:

• chr4-76306899-C-T
• NM_003943.5:c.130C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00600
• Publications: 0 publications found

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]

ENSG00000287401 (HGNC:):

ACMG classification

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

Sel.	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.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460304 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726442

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25970

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5518

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60282

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.0060
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.090
Sift	Benign	0.091	T
Sift4G	Benign	0.11	T
Polyphen		0.70	P
Vest4		0.016
MutPred		0.10		Gain of methylation at K40 (P = 0.15)
MVP		0.15
MPC		0.16
ClinPred		0.21	T
GERP RS		0.52
PromoterAI		0.0013	Neutral
Varity_R		0.048
gMVP		0.062
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr4-77228052;