chr11-8038924-G-C

Position:

• chr11-8038924-G-C

Variant summary

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

The NM_003320.5(TUB):​c.51G>C​(p.Glu17Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TUB NM_003320.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 2.73

Genes affected

TUB (HGNC:12406): (TUB bipartite transcription factor) This gene encodes a member of the Tubby family of bipartite transcription factors. The encoded protein may play a role in obesity and sensorineural degradation. The crystal structure has been determined for a similar protein in mouse, and it functions as a membrane-bound transcription regulator that translocates to the nucleus in response to phosphoinositide hydrolysis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ENSG00000254921 (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=0.13581216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TUB	NM_003320.5	c.51G>C	p.Glu17Asp	missense_variant	1/13		NP_003311.2
TUB	XM_005253109.4	c.164+19566G>C		intron_variant			XP_005253166.1
TUB	XM_047427512.1	c.164+19566G>C		intron_variant			XP_047283468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TUB	ENST00000305253.8	c.51G>C	p.Glu17Asp	missense_variant	1/13	1		ENSP00000305426.4
TUB	ENST00000534099.5	c.56+19566G>C		intron_variant		2		ENSP00000434400.1
ENSG00000254921	ENST00000528151.1	n.262C>G		non_coding_transcript_exon_variant	2/2	4
ENSG00000254921	ENST00000526646.2	n.202+593C>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinal dystrophy Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.078
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.63	T
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.19
Sift	Benign	0.24	T
Sift4G	Benign	0.17	T
Polyphen		0.0070	B
Vest4		0.20
MutPred		0.23		Gain of sheet (P = 0.0477);
MVP		0.86
MPC		0.16
ClinPred		0.91	D
GERP RS		3.0
gMVP		0.033

Splicing

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: chr11-8060471;