rs1893261

chr11-120327384-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000529187.1(TLCD5):c.9G>A(p.Gln3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,612,038 control chromosomes in the GnomAD database, including 120,016 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (12265 hom., cov: 33)
  • Exomes 𝑓: 0.38 (107751 hom.)
• Consequence: TLCD5 ENST00000529187.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701

Genes affected

TLCD5 (HGNC:28280): (TLC domain containing 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.701 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLCD5	NM_001198671.2	c.-1-57G>A		intron_variant		ENST00000375095.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLCD5	ENST00000375095.3	c.-1-57G>A		intron_variant		2	NM_001198671.2	P1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60498 AN: 152000 Hom.: 12249 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.379

GnomAD3 exomes AF: 0.389 AC: 97580 AN: 251076 Hom.: 19278 AF XY: 0.392 AC XY: 53148 AN XY: 135692

Gnomad AFR exome AF: 0.437

Gnomad AMR exome AF: 0.347

Gnomad ASJ exome AF: 0.407

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.454

Gnomad FIN exome AF: 0.467

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.382 AC: 557611 AN: 1459920 Hom.: 107751 Cov.: 37 AF XY: 0.384 AC XY: 278912 AN XY: 726358

Gnomad4 AFR exome AF: 0.436

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.375

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.398 AC: 60549 AN: 152118 Hom.: 12265 Cov.: 33 AF XY: 0.401 AC XY: 29782 AN XY: 74354

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.374

Alfa AF: 0.379 Hom.: 15096

Bravo AF: 0.386

Asia WGS AF: 0.428 AC: 1488 AN: 3478

EpiCase AF: 0.367

EpiControl AF: 0.371

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.3
Dann	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1893261; hg19: chr11-120198093; COSMIC: COSV58754915;