chr16-30025214-C-G

Variant names:

• chr16-30025214-C-G
• rs775568160
• NM_031478.6:c.794G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_031478.6(TLCD3B):​c.794G>C​(p.Arg265Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000743 in 1,346,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R265W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TLCD3B NM_031478.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.523
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08788574).
• BP6: Variant 16-30025214-C-G is Benign according to our data. Variant chr16-30025214-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3807175.Status of the report is criteria_provided_single_submitter, 1 stars.

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.794G>C	p.Arg265Pro	missense	Exon 5 of 5	NP_113666.2	Q71RH2-1
	TLCD3B	NM_001352173.2		c.1052G>C	p.Arg351Pro	missense	Exon 6 of 6	NP_001339102.1
	TLCD3B	NM_001318504.2		c.644G>C	p.Arg215Pro	missense	Exon 5 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.794G>C	p.Arg265Pro	missense	Exon 5 of 5	ENSP00000369863.4	Q71RH2-1
	TLCD3B	ENST00000279389.8	TSL:1	c.644G>C	p.Arg215Pro	missense	Exon 5 of 5	ENSP00000279389.4	Q71RH2-2
	TLCD3B	ENST00000934494.1		c.791G>C	p.Arg264Pro	missense	Exon 5 of 5	ENSP00000604553.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1346138 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 660964

African (AFR) AF: 0.00 AC: 0 AN: 28996

American (AMR) AF: 0.00 AC: 0 AN: 23534

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35178

South Asian (SAS) AF: 0.00 AC: 0 AN: 71418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1059966

Other (OTH) AF: 0.00 AC: 0 AN: 55668

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.077
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	N
PhyloP100		0.52
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.036
Sift	Benign	0.28	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.095
MutPred		0.43		Gain of glycosylation at R265 (P = 8e-04)
MVP		0.20
MPC		0.71
ClinPred		0.20	T
GERP RS		1.7
Varity_R		0.28
gMVP		0.45

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: rs775568160; hg19: chr16-30036535;