11-120327602-T-G

Variant names:

• chr11-120327602-T-G
• rs368599021
• NM_001198671.2:c.161T>G

Variant summary

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

The NM_001198671.2(TLCD5):​c.161T>G​(p.Ile54Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I54T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TLCD5 NM_001198671.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198671.2. 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
	TLCD5	NM_001198671.2	MANE Select	c.161T>G	p.Ile54Ser	missense	Exon 2 of 3	NP_001185600.1	Q6ZRR5-1
	TLCD5	NM_001198670.2		c.227T>G	p.Ile76Ser	missense	Exon 2 of 3	NP_001185599.1	Q6ZRR5-3
	TLCD5	NM_174926.3		c.227T>G	p.Ile76Ser	missense	Exon 2 of 4	NP_777586.1	Q6ZRR5-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD5	ENST00000375095.3	TSL:2 MANE Select	c.161T>G	p.Ile54Ser	missense	Exon 2 of 3	ENSP00000364236.3	Q6ZRR5-1
	TLCD5	ENST00000529187.1	TSL:1	c.227T>G	p.Ile76Ser	missense	Exon 2 of 4	ENSP00000434862.1	Q6ZRR5-4
	TLCD5	ENST00000314475.6	TSL:2	c.227T>G	p.Ile76Ser	missense	Exon 2 of 3	ENSP00000312672.2	Q6ZRR5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Benign	1.7	L
PhyloP100		8.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.7	N
REVEL	Pathogenic	0.78
Sift	Benign	0.11	T
Sift4G	Uncertain	0.012	D
Polyphen		0.082	B
Vest4		0.85
MutPred		0.70		Loss of sheet (P = 0.0084)
MVP		0.83
MPC		0.14
ClinPred		0.89	D
GERP RS		5.6
Varity_R		0.35
gMVP		0.82
Mutation Taster		=60/40	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: rs368599021; hg19: chr11-120198311;