11-120327580-T-A

Variant names:

• chr11-120327580-T-A
• rs374558383
• NM_001198671.2:c.139T>A

Variant summary

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

The NM_001198671.2(TLCD5):​c.139T>A​(p.Ser47Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S47P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TLCD5 NM_001198671.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21284541).

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.139T>A	p.Ser47Thr	missense	Exon 2 of 3	NP_001185600.1	Q6ZRR5-1
	TLCD5	NM_001198670.2		c.205T>A	p.Ser69Thr	missense	Exon 2 of 3	NP_001185599.1	Q6ZRR5-3
	TLCD5	NM_174926.3		c.205T>A	p.Ser69Thr	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.139T>A	p.Ser47Thr	missense	Exon 2 of 3	ENSP00000364236.3	Q6ZRR5-1
	TLCD5	ENST00000529187.1	TSL:1	c.205T>A	p.Ser69Thr	missense	Exon 2 of 4	ENSP00000434862.1	Q6ZRR5-4
	TLCD5	ENST00000314475.6	TSL:2	c.205T>A	p.Ser69Thr	missense	Exon 2 of 3	ENSP00000312672.2	Q6ZRR5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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: 0.00000180 AC: 2 AN: 1112008

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	Benign	0.13
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.0060
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.40	N
REVEL	Uncertain	0.29
Sift	Benign	0.33	T
Sift4G	Benign	0.55	T
Polyphen		0.026	B
Vest4		0.30
MutPred		0.57		Loss of sheet (P = 0.0025)
MVP		0.84
MPC		0.089
ClinPred		0.22	T
GERP RS		5.6
Varity_R		0.052
gMVP		0.47
Mutation Taster		=85/15	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: rs374558383; hg19: chr11-120198289;