chr7-93994306-G-T

Position:

• chr7-93994306-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005868.6(BET1):​c.281C>A​(p.Thr94Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BET1 NM_005868.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.64

Genes affected

BET1 (HGNC:14562): (Bet1 golgi vesicular membrane trafficking protein) This gene encodes a golgi-associated membrane protein that participates in vesicular transport from the endoplasmic reticulum (ER) to the Golgi complex. The encoded protein functions as a soluble N-ethylaleimide-sensitive factor attachment protein receptor and may be involved in the docking of ER-derived vesicles with the cis-Golgi membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

BET1-AS1 (HGNC:40690): (BET1 antisense RNA 1)

LOC107986820 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16323182).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BET1	NM_005868.6	c.281C>A	p.Thr94Lys	missense_variant	4/4	ENST00000222547.8	NP_005859.1
LOC107986820	XR_001745270.3	n.4248+2140G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BET1	ENST00000222547.8	c.281C>A	p.Thr94Lys	missense_variant	4/4	1	NM_005868.6	ENSP00000222547	P1
BET1-AS1	ENST00000426634.1	n.481+2140G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.281C>A (p.T94K) alteration is located in exon 4 (coding exon 4) of the BET1 gene. This alteration results from a C to A substitution at nucleotide position 281, causing the threonine (T) at amino acid position 94 to be replaced by a lysine (K). 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	0.47
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.82
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.15
Sift	Benign	0.96	T
Sift4G	Benign	0.93	T
Polyphen		0.019	B
Vest4		0.45
MutPred		0.39		Gain of methylation at T94 (P = 0.014);
MVP		0.30
MPC		0.21
ClinPred		0.51	D
GERP RS		3.3
Varity_R		0.11
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-93623618;