Genetic Variant TLCD5:p.Asn137Ser (chr11-120330187-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001198671.2(TLCD5):c.410A>G(p.Asn137Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,578,496 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 5 hom. )

Consequence

TLCD5
NM_001198671.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

Publications

2 publications found

Variant links:

Genes affected

TLCD5 (HGNC:28280): (TLC domain containing 5) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TLCD5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.072579324).

BS2

High Homozygotes in GnomAdExome4 at 5 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD5	NM_001198671.2	MANE Select	c.410A>G	p.Asn137Ser	missense	Exon 3 of 3	NP_001185600.1	Q6ZRR5-1
TLCD5	NM_001198670.2		c.476A>G	p.Asn159Ser	missense	Exon 3 of 3	NP_001185599.1	Q6ZRR5-3
TLCD5	NM_001198672.2		c.107A>G	p.Asn36Ser	missense	Exon 3 of 3	NP_001185601.1	A8K0W5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD5	ENST00000375095.3	TSL:2 MANE Select	c.410A>G	p.Asn137Ser	missense	Exon 3 of 3	ENSP00000364236.3	Q6ZRR5-1
TLCD5	ENST00000529187.1	TSL:1	c.338+138A>G		intron	N/A	ENSP00000434862.1	Q6ZRR5-4
TLCD5	ENST00000314475.6	TSL:2	c.476A>G	p.Asn159Ser	missense	Exon 3 of 3	ENSP00000312672.2	Q6ZRR5-3

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000419

AC:

AN:

193328

AF XY:

0.000514

show subpopulations

Gnomad AFR exome

AF:

0.0000832

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00154

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000616

Gnomad OTH exome

AF:

0.000579

GnomAD4 exome

AF:

0.000234

AC:

334

AN:

1426326

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

207

AN XY:

706228

show subpopulations

African (AFR)

AF:

0.0000304

AC:

AN:

32898

American (AMR)

AF:

0.0000782

AC:

AN:

38356

Ashkenazi Jewish (ASJ)

AF:

0.00180

AC:

AN:

25544

East Asian (EAS)

AF:

0.00

AC:

AN:

38454

South Asian (SAS)

AF:

0.00254

AC:

210

AN:

82700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50176

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.0000476

AC:

AN:

1093214

Other (OTH)

AF:

0.000236

AC:

AN:

59258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41514

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00291

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68008

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000470

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000338

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.035

MetaRNN

Benign

0.073

MetaSVM

Uncertain

0.0014

MutationAssessor

Benign

1.9

PhyloP100

9.2

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.60

Sift

Benign

0.095

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.74

MVP

0.70

MPC

0.41

ClinPred

0.076

GERP RS

4.9

Varity_R

0.17

gMVP

0.81

Mutation Taster

=87/13

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over