rs537230252

Variant names:

• chr19-507655-C-A
• rs537230252
• NM_033513.3:c.149C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-507655-C-A
• chr19-507655-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033513.3(TPGS1):​c.149C>A​(p.Ala50Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,239,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A50V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: TPGS1 NM_033513.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

Genes affected

TPGS1 (HGNC:25058): (tubulin polyglutamylase complex subunit 1) Predicted to enable microtubule binding activity. Predicted to be involved in protein polyglutamylation. Predicted to act upstream of or within several processes, including adult behavior; chemical synaptic transmission; and sperm axoneme assembly. Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

MADCAM1-AS1 (HGNC:55315): (MADCAM1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15564889).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033513.3. 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
	TPGS1	NM_033513.3	MANE Select	c.149C>A	p.Ala50Glu	missense	Exon 1 of 2	NP_277048.2	Q6ZTW0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPGS1	ENST00000359315.6	TSL:1 MANE Select	c.149C>A	p.Ala50Glu	missense	Exon 1 of 2	ENSP00000352265.4	Q6ZTW0-1
	TPGS1	ENST00000588278.1	TSL:6	n.156C>A		non_coding_transcript_exon	Exon 1 of 1
	MADCAM1-AS1	ENST00000592413.2	TSL:5	n.179G>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1239640 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 603386

African (AFR) AF: 0.00 AC: 0 AN: 25266

American (AMR) AF: 0.00 AC: 0 AN: 16804

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19000

East Asian (EAS) AF: 0.00 AC: 0 AN: 27940

South Asian (SAS) AF: 0.00 AC: 0 AN: 60490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44054

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5034

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 991202

Other (OTH) AF: 0.0000201 AC: 1 AN: 49850

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.60	T
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.030	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	0.51	T
Polyphen		0.34	B
Vest4		0.17
MutPred		0.32		Gain of ubiquitination at K54 (P = 0.0931)
MVP		0.80
MPC		0.99
ClinPred		0.32	T
GERP RS		4.1
PromoterAI		0.092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.29
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs537230252; hg19: chr19-507655;