rs763015790

Variant names:

• chr16-30026712-G-A
• rs763015790
• NM_031478.6:c.341C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-30026712-G-A
• chr16-30026712-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031478.6(TLCD3B):​c.341C>T​(p.Ala114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TLCD3B NM_031478.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 1 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10181117).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD3B	NM_031478.6	MANE Select	c.341C>T	p.Ala114Val	missense	Exon 3 of 5	NP_113666.2	Q71RH2-1
	TLCD3B	NM_001352173.2		c.599C>T	p.Ala200Val	missense	Exon 4 of 6	NP_001339102.1
	TLCD3B	NM_001318504.2		c.191C>T	p.Ala64Val	missense	Exon 3 of 5	NP_001305433.1	Q71RH2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TLCD3B	ENST00000380495.9	TSL:1 MANE Select	c.341C>T	p.Ala114Val	missense	Exon 3 of 5	ENSP00000369863.4	Q71RH2-1
	TLCD3B	ENST00000279389.8	TSL:1	c.191C>T	p.Ala64Val	missense	Exon 3 of 5	ENSP00000279389.4	Q71RH2-2
	TLCD3B	ENST00000934494.1		c.341C>T	p.Ala114Val	missense	Exon 3 of 5	ENSP00000604553.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250506 AF XY: 0.00

Gnomad AFR exome AF: 0.0000618

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: 0.00000274 AC: 4 AN: 1461676 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 727146

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53244

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.072
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.032
Sift	Benign	0.34	T
Sift4G	Benign	0.23	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.24		Loss of disorder (P = 0.0365)
MVP		0.29
MPC		0.49
ClinPred		0.096	T
GERP RS		4.9
Varity_R		0.040
gMVP		0.57
Mutation Taster		=94/6	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: rs763015790; hg19: chr16-30038033;