NM_001198671.2:c.431G>C

Variant names:

• chr11-120330208-G-C
• NM_001198671.2:c.431G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001198671.2(TLCD5):​c.431G>C​(p.Trp144Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TLCD5 NM_001198671.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.87
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

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.431G>C	p.Trp144Ser	missense	Exon 3 of 3	NP_001185600.1	Q6ZRR5-1
	TLCD5	NM_001198670.2		c.497G>C	p.Trp166Ser	missense	Exon 3 of 3	NP_001185599.1	Q6ZRR5-3
	TLCD5	NM_001198672.2		c.128G>C	p.Trp43Ser	missense	Exon 3 of 3	NP_001185601.1	A8K0W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD5	ENST00000375095.3	TSL:2 MANE Select	c.431G>C	p.Trp144Ser	missense	Exon 3 of 3	ENSP00000364236.3	Q6ZRR5-1
	TLCD5	ENST00000529187.1	TSL:1	c.338+159G>C		intron	N/A	ENSP00000434862.1	Q6ZRR5-4
	TLCD5	ENST00000314475.6	TSL:2	c.497G>C	p.Trp166Ser	missense	Exon 3 of 3	ENSP00000312672.2	Q6ZRR5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	D
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.98
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.58	D
MutationAssessor	Uncertain	2.3	M
PhyloP100		9.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.66		Gain of disorder (P = 0.0027)
MVP		0.93
MPC		0.58
ClinPred		1.0	D
GERP RS		6.1
Varity_R		0.96
gMVP		0.95
Mutation Taster		=2/98	disease causing

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

hg19: chr11-120200917;