Genetic Variant NM_031478.6:c.794_801dupGGCCGCCC (chr16-30025206-G-GGGGCGGCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_031478.6(TLCD3B):c.794_801dupGGCCGCCC(p.Pro268GlyfsTer96) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,490,616 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

TLCD3B
NM_031478.6 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.459

Publications

0 publications found

Variant links:

Genes affected

TLCD3B (HGNC:25295): (TLC domain containing 3B) This gene encodes a transmembrane protein, which may be a likely target of peroxisome proliferator-activated receptor gamma (PPAR-gamma). The product of the orthologous gene in mouse is related to obesity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TLCD3B links:

C16orf92 (HGNC:26346): (chromosome 16 open reading frame 92) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

C16orf92 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 48 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031478.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD3B	NM_031478.6	MANE Select	c.794_801dupGGCCGCCC	p.Pro268GlyfsTer96	frameshift	Exon 5 of 5	NP_113666.2	Q71RH2-1
TLCD3B	NM_001352173.2		c.1052_1059dupGGCCGCCC	p.Pro354GlyfsTer96	frameshift	Exon 6 of 6	NP_001339102.1
TLCD3B	NM_001318504.2		c.644_651dupGGCCGCCC	p.Pro218GlyfsTer96	frameshift	Exon 5 of 5	NP_001305433.1	Q71RH2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TLCD3B	ENST00000380495.9	TSL:1 MANE Select	c.794_801dupGGCCGCCC	p.Pro268GlyfsTer96	frameshift	Exon 5 of 5	ENSP00000369863.4	Q71RH2-1
TLCD3B	ENST00000279389.8	TSL:1	c.644_651dupGGCCGCCC	p.Pro218GlyfsTer96	frameshift	Exon 5 of 5	ENSP00000279389.4	Q71RH2-2
TLCD3B	ENST00000934494.1		c.791_798dupGGCCGCCC	p.Pro267GlyfsTer96	frameshift	Exon 5 of 5	ENSP00000604553.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000523

AC:

AN:

95524

AF XY:

0.0000781

show subpopulations

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:

0.0000978

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000351

GnomAD4 exome

AF:

0.0000359

AC:

AN:

1338490

Hom.:

Cov.:

AF XY:

0.0000533

AC XY:

AN XY:

656538

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28850

American (AMR)

AF:

0.000132

AC:

AN:

22810

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21536

East Asian (EAS)

AF:

0.00

AC:

AN:

35208

South Asian (SAS)

AF:

0.000230

AC:

AN:

69524

European-Finnish (FIN)

AF:

0.0000227

AC:

AN:

43992

Middle Eastern (MID)

AF:

0.000251

AC:

AN:

3992

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

1057208

Other (OTH)

AF:

0.0000903

AC:

AN:

55370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000263

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000843

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone-rod dystrophy 22 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.46

Mutation Taster

=37/163

disease causing

(source)

Splicing

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