16-3299545-C-T

Variant names:

• chr16-3299545-C-T
• rs1337825325
• NM_033208.4:c.1070G>A

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.1070G>A​(p.Ser357Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,526,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TIGD7 NM_033208.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.848
• Publications: 0 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=0.09497082).

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.1070G>A	p.Ser357Asn	missense	Exon 2 of 2	NP_149985.2
	ZNF263	NM_001411015.1		c.*46+389C>T		intron	N/A	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.1070G>A	p.Ser357Asn	missense	Exon 2 of 2	ENSP00000380071.1	Q6NT04-1
	TIGD7	ENST00000903484.1		c.1070G>A	p.Ser357Asn	missense	Exon 2 of 2	ENSP00000573543.1
	TIGD7	ENST00000903485.1		c.1070G>A	p.Ser357Asn	missense	Exon 2 of 2	ENSP00000573544.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152046 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1374180 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675860

African (AFR) AF: 0.00 AC: 0 AN: 30020

American (AMR) AF: 0.00 AC: 0 AN: 27532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21472

East Asian (EAS) AF: 0.00 AC: 0 AN: 38182

South Asian (SAS) AF: 0.00 AC: 0 AN: 71542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50704

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5390

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1072988

Other (OTH) AF: 0.00 AC: 0 AN: 56350

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152046 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41358

American (AMR) AF: 0.00 AC: 0 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

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

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	0.082
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.073
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N
PhyloP100		0.85
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.046
Sift	Uncertain	0.024	D
Sift4G	Benign	0.16	T
Polyphen		0.43	B
Vest4		0.10
MutPred		0.38		Loss of phosphorylation at S357 (P = 0.0244)
MVP		0.25
MPC		0.31
ClinPred		0.64	D
GERP RS		3.8
Varity_R		0.082
gMVP		0.053
Mutation Taster		=93/7	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: rs1337825325; hg19: chr16-3349545;