rs748551548

Variant names:

• chr11-8038946-G-A
• ENST00000305253.8:c.73G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-8038946-G-A
• chr11-8038946-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003320.5(TUB):​c.73G>A​(p.Gly25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TUB NM_003320.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32646918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUB	NM_003320.5	c.73G>A	p.Gly25Ser	missense_variant	Exon 1 of 13		NP_003311.2
TUB	XM_005253109.4	c.164+19588G>A		intron_variant	Intron 1 of 11		XP_005253166.1
TUB	XM_047427512.1	c.164+19588G>A		intron_variant	Intron 1 of 11		XP_047283468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUB	ENST00000305253.8	c.73G>A	p.Gly25Ser	missense_variant	Exon 1 of 13	1		ENSP00000305426.4
TUB	ENST00000534099.5	c.56+19588G>A		intron_variant	Intron 1 of 11	2		ENSP00000434400.1
ENSG00000254921	ENST00000528151.1	n.240C>T		non_coding_transcript_exon_variant	Exon 2 of 2	4
ENSG00000254921	ENST00000526646.2	n.202+571C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461814 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727214

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	1.0
Eigen	Benign	-0.0025
Eigen_PC	Benign	0.074
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.53	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.091	T
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.28
Sift	Uncertain	0.018	D
Sift4G	Benign	0.28	T
Polyphen		0.45	B
Vest4		0.37
MutPred		0.24		Gain of glycosylation at G25 (P = 0.0062);
MVP		0.89
MPC		0.18
ClinPred		0.83	D
GERP RS		3.8
gMVP		0.058

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: chr11-8060493;