rs148645230

Variant names:

• chr18-12325203-G-A
• rs148645230
• NM_032525.3:c.414G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-12325203-G-A
• chr18-12325203-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_032525.3(TUBB6):​c.414G>A​(p.Ser138Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,614,092 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (7 hom.)
• Consequence: TUBB6 NM_032525.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.748
• Publications: 2 publications found

Genes affected

TUBB6 (HGNC:20776): (tubulin beta 6 class V) Predicted to enable GTP binding activity. Predicted to be a structural constituent of cytoskeleton. Predicted to be involved in microtubule cytoskeleton organization and mitotic cell cycle. Located in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

TUBB6 Gene-Disease associations (from GenCC):

• facial palsy, congenital, with ptosis and velopharyngeal dysfunction

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007141024).
• BP6: Variant 18-12325203-G-A is Benign according to our data. Variant chr18-12325203-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3053443.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.748 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032525.3. 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
	TUBB6	NM_032525.3	MANE Select	c.414G>A	p.Ser138Ser	synonymous	Exon 4 of 4	NP_115914.1	Q9BUF5
	TUBB6	NM_001303524.1		c.414G>A	p.Ser138Ser	synonymous	Exon 5 of 5	NP_001290453.1	Q9BUF5
	TUBB6	NM_001303526.2		c.303G>A	p.Ser101Ser	synonymous	Exon 3 of 3	NP_001290455.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TUBB6	ENST00000317702.10	TSL:1 MANE Select	c.414G>A	p.Ser138Ser	synonymous	Exon 4 of 4	ENSP00000318697.4	Q9BUF5
	TUBB6	ENST00000591909.5	TSL:1	c.278-3943G>A		intron	N/A	ENSP00000465040.1	K7EJ64
	TUBB6	ENST00000586810.5	TSL:1	n.*455G>A		non_coding_transcript_exon	Exon 5 of 5	ENSP00000467348.1	K7EPE5

Frequencies

GnomAD3 genomes AF: 0.00151 AC: 230 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00237

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00151 AC: 379 AN: 251252 AF XY: 0.00160

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00248

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00231

Gnomad NFE exome AF: 0.00222

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00164 AC: 2398 AN: 1461774 Hom.: 7 Cov.: 31 AF XY: 0.00164 AC XY: 1195 AN XY: 727206

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.000403 AC: 18 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000788 AC: 68 AN: 86242

European-Finnish (FIN) AF: 0.00225 AC: 120 AN: 53386

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.00184 AC: 2044 AN: 1111980

Other (OTH) AF: 0.00149 AC: 90 AN: 60394

GnomAD4 genome AF: 0.00151 AC: 230 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00150 AC XY: 112 AN XY: 74484

African (AFR) AF: 0.000481 AC: 20 AN: 41580

American (AMR) AF: 0.000719 AC: 11 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00237 AC: 161 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.00179 Hom.: 1

Bravo AF: 0.00138

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00349 AC: 30

ExAC AF: 0.00154 AC: 187

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00218

EpiControl AF: 0.00219

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TUBB6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	8.5
DANN	Benign	0.94
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.0071	T
PhyloP100		-0.75
Sift4G	Benign	0.092	T
Vest4		0.11
MVP		0.84
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=91/9	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

dbSNP: rs148645230; hg19: chr18-12325202;