chr11-120330114-A-G

Variant names:

• chr11-120330114-A-G
• rs768044932
• NM_001198671.2:c.337A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001198671.2(TLCD5):​c.337A>G​(p.Ile113Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: TLCD5 NM_001198671.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.98
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4072879).

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.337A>G	p.Ile113Val	missense	Exon 3 of 3	NP_001185600.1	Q6ZRR5-1
	TLCD5	NM_001198670.2		c.403A>G	p.Ile135Val	missense	Exon 3 of 3	NP_001185599.1	Q6ZRR5-3
	TLCD5	NM_001198672.2		c.34A>G	p.Ile12Val	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.337A>G	p.Ile113Val	missense	Exon 3 of 3	ENSP00000364236.3	Q6ZRR5-1
	TLCD5	ENST00000529187.1	TSL:1	c.338+65A>G		intron	N/A	ENSP00000434862.1	Q6ZRR5-4
	TLCD5	ENST00000314475.6	TSL:2	c.403A>G	p.Ile135Val	missense	Exon 3 of 3	ENSP00000312672.2	Q6ZRR5-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251014 AF XY: 0.0000590

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000151 AC: 22 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727162

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

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

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

South Asian (SAS) AF: 0.000244 AC: 21 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111962

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000247 AC: 3

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	Benign	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.42
Sift	Benign	0.030	D
Sift4G	Benign	0.075	T
Polyphen		0.75	P
Vest4		0.53
MutPred		0.55		Gain of catalytic residue at I113 (P = 0.0029)
MVP		0.55
MPC		0.099
ClinPred		0.23	T
GERP RS		6.1
Varity_R		0.15
gMVP		0.52
Mutation Taster		=82/18	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: rs768044932; hg19: chr11-120200823;