chr16-3299121-C-G

Variant names:

• chr16-3299121-C-G
• rs771286715
• NM_033208.4:c.1494G>C

Variant summary

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

The NM_033208.4(TIGD7):​c.1494G>C​(p.Gln498His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000716 in 1,467,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000074 (0 hom.)
• Consequence: TIGD7 NM_033208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.259
• Publications: 1 publications found

Genes affected

TIGD7 (HGNC:18331): (tigger transposable element derived 7) The protein encoded by this gene belongs to the tigger subfamily of the pogo superfamily of DNA-mediated transposons in humans. These proteins are related to DNA transposons found in fungi and nematodes, and more distantly to the Tc1 and mariner transposases. They are also very similar to the major mammalian centromere protein B. The exact function of this gene is not known. [provided by RefSeq, Jul 2008]

ZNF263 (HGNC:13056): (zinc finger protein 263) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and transcription cis-regulatory region binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleus. [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=0.14734802).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033208.4. 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
	TIGD7	NM_033208.4	MANE Select	c.1494G>C	p.Gln498His	missense	Exon 2 of 2	NP_149985.2
	ZNF263	NM_001411015.1		c.*11C>G		3_prime_UTR	Exon 7 of 8	NP_001397944.1	D3DUC1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD7	ENST00000396862.2	TSL:2 MANE Select	c.1494G>C	p.Gln498His	missense	Exon 2 of 2	ENSP00000380071.1	Q6NT04-1
	TIGD7	ENST00000903484.1		c.1494G>C	p.Gln498His	missense	Exon 2 of 2	ENSP00000573543.1
	TIGD7	ENST00000903485.1		c.1494G>C	p.Gln498His	missense	Exon 2 of 2	ENSP00000573544.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 32

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000730 AC: 11 AN: 150644 AF XY: 0.0000744

Gnomad AFR exome AF: 0.0000814

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: 0.000115

Gnomad OTH exome AF: 0.000324

GnomAD4 exome AF: 0.0000738 AC: 97 AN: 1315008 Hom.: 0 Cov.: 30 AF XY: 0.0000762 AC XY: 49 AN XY: 643376

African (AFR) AF: 0.0000724 AC: 2 AN: 27610

American (AMR) AF: 0.00 AC: 0 AN: 22630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19202

East Asian (EAS) AF: 0.00 AC: 0 AN: 34784

South Asian (SAS) AF: 0.00 AC: 0 AN: 60048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5194

European-Non Finnish (NFE) AF: 0.0000863 AC: 90 AN: 1042980

Other (OTH) AF: 0.0000928 AC: 5 AN: 53890

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000662 AC: 8

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.031
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.26
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.091
Sift	Uncertain	0.022	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.27		Gain of helix (P = 0.0199)
MVP		0.14
MPC		0.061
ClinPred		0.044	T
GERP RS		1.5
Varity_R		0.057
gMVP		0.099
Mutation Taster		=95/5	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: rs771286715; hg19: chr16-3349121; COSMIC: COSV51916988; COSMIC: COSV51916988;