chr11-120327384-G-A

Variant names:

• chr11-120327384-G-A
• rs1893261
• ENST00000529187.1:c.9G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000529187.1(TLCD5):​c.9G>A​(p.Gln3Gln) 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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000529187.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD5	NM_001198671.2	MANE Select	c.-1-57G>A		intron	N/A	NP_001185600.1
	TLCD5	NM_001198670.2		c.9G>A	p.Gln3Gln	synonymous	Exon 2 of 3	NP_001185599.1
	TLCD5	NM_174926.3		c.9G>A	p.Gln3Gln	synonymous	Exon 2 of 4	NP_777586.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD5	ENST00000529187.1	TSL:1	c.9G>A	p.Gln3Gln	synonymous	Exon 2 of 4	ENSP00000434862.1
	TLCD5	ENST00000375095.3	TSL:2 MANE Select	c.-1-57G>A		intron	N/A	ENSP00000364236.3
	TLCD5	ENST00000314475.6	TSL:2	c.9G>A	p.Gln3Gln	synonymous	Exon 2 of 3	ENSP00000312672.2

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

GnomAD2 exomes AF: 0.389 AC: 97580 AN: 251076 AF XY: 0.392

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 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

African (AFR) AF: 0.436 AC: 14573 AN: 33388

American (AMR) AF: 0.352 AC: 15711 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 10474 AN: 26070

East Asian (EAS) AF: 0.268 AC: 10655 AN: 39692

South Asian (SAS) AF: 0.450 AC: 38805 AN: 86172

European-Finnish (FIN) AF: 0.471 AC: 25158 AN: 53414

Middle Eastern (MID) AF: 0.357 AC: 1968 AN: 5508

European-Non Finnish (NFE) AF: 0.375 AC: 416734 AN: 1110696

Other (OTH) AF: 0.390 AC: 23533 AN: 60318

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

African (AFR) AF: 0.439 AC: 18188 AN: 41466

American (AMR) AF: 0.354 AC: 5416 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1453 AN: 5180

South Asian (SAS) AF: 0.471 AC: 2270 AN: 4822

European-Finnish (FIN) AF: 0.472 AC: 5001 AN: 10588

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25656 AN: 67982

Other (OTH) AF: 0.374 AC: 789 AN: 2112

Alfa AF: 0.381 Hom.: 20489

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.28
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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