11-120330054-G-T

Variant names:

• chr11-120330054-G-T
• NM_001198671.2:c.277G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001198671.2(TLCD5):​c.277G>T​(p.Val93Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 0.149

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16968909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TLCD5	NM_001198671.2	c.277G>T	p.Val93Phe	missense_variant	Exon 3 of 3	ENST00000375095.3	NP_001185600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TLCD5	ENST00000375095.3	c.277G>T	p.Val93Phe	missense_variant	Exon 3 of 3	2	NM_001198671.2	ENSP00000364236.3
TLCD5	ENST00000529187.1	c.338+5G>T		splice_region_variant, intron_variant	Intron 3 of 3	1		ENSP00000434862.1
TLCD5	ENST00000314475.6	c.343G>T	p.Val115Phe	missense_variant	Exon 3 of 3	2		ENSP00000312672.2
TLCD5	ENST00000531346.1	n.151G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.46	T;.
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N;N
REVEL	Uncertain	0.44
Sift	Benign	0.037	D;D
Sift4G	Benign	0.19	T;T
Polyphen		0.013	B;B
Vest4		0.40
MutPred		0.33		Loss of sheet (P = 0.007);.;
MVP		0.20
MPC		0.12
ClinPred		0.11	T
GERP RS		-5.0
Varity_R		0.11
gMVP		0.75

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-120200763;