19-48897377-C-T

Position:

• chr19-48897377-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003323.3(TULP2):​c.52G>A​(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,613,196 control chromosomes in the GnomAD database, including 16,713 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.18 (3115 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13598 hom.)
• Consequence: TULP2 NM_003323.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

Genes affected

TULP2 (HGNC:12424): (TUB like protein 2) TULP2 is a member of a family of tubby-like genes (TULPs) that encode proteins of unknown function. Members of this family have been identified in plants, vertebrates, and invertebrates. The TULP proteins share a conserved C-terminal region of approximately 200 amino acid residues. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TULP2	NM_003323.3	c.52G>A	p.Ala18Thr	missense_variant	3/13	ENST00000221399.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TULP2	ENST00000221399.8	c.52G>A	p.Ala18Thr	missense_variant	3/13	1	NM_003323.3	P2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27558 AN: 151972 Hom.: 3108 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0711

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.190

GnomAD3 exomes AF: 0.148 AC: 37035 AN: 249958 Hom.: 3136 AF XY: 0.145 AC XY: 19575 AN XY: 135172

Gnomad AFR exome AF: 0.323

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.0696

Gnomad SAS exome AF: 0.185

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.147

GnomAD4 exome AF: 0.129 AC: 188684 AN: 1461106 Hom.: 13598 Cov.: 32 AF XY: 0.130 AC XY: 94677 AN XY: 726830

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0687

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.181 AC: 27592 AN: 152090 Hom.: 3115 Cov.: 32 AF XY: 0.181 AC XY: 13486 AN XY: 74356

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0707

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.188

Alfa AF: 0.127 Hom.: 3605

Bravo AF: 0.189

TwinsUK AF: 0.114 AC: 423

ALSPAC AF: 0.118 AC: 453

ESP6500AA AF: 0.315 AC: 1386

ESP6500EA AF: 0.120 AC: 1029

ExAC AF: 0.150 AC: 18262

Asia WGS AF: 0.135 AC: 471 AN: 3478

EpiCase AF: 0.118

EpiControl AF: 0.118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.1
DANN	Benign	0.74
DEOGEN2	Benign	0.0054	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.40	T;T;T
MetaRNN	Benign	0.0043	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.60	T;T;T
Sift4G	Benign	0.46	T;.;.
Polyphen		0.062	B;.;.
Vest4		0.015
MPC		1.0
ClinPred		0.00070	T
GERP RS		-0.41
Varity_R		0.036
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: 19

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7260579; hg19: chr19-49400634; COSMIC: COSV54387530; COSMIC: COSV54387530;