16-3298996-C-T

Variant names:

• chr16-3298996-C-T
• rs144459500
• NM_033208.4:c.1619G>A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033208.4(TIGD7):​c.1619G>A​(p.Ser540Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,322,196 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S540G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (3 hom.)
• Consequence: TIGD7 NM_033208.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.836

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028523505).
• BP6: Variant 16-3298996-C-T is Benign according to our data. Variant chr16-3298996-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2393130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIGD7	NM_033208.4	c.1619G>A	p.Ser540Asn	missense_variant	Exon 2 of 2	ENST00000396862.2	NP_149985.2
ZNF263	NM_001411015.1	c.2048-110C>T		intron_variant	Intron 6 of 7		NP_001397944.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIGD7	ENST00000396862.2	c.1619G>A	p.Ser540Asn	missense_variant	Exon 2 of 2	2	NM_033208.4	ENSP00000380071.1
ZNF263	ENST00000574674.2	c.2048-110C>T		intron_variant	Intron 6 of 7	2		ENSP00000461755.2
ZNF263	ENST00000575332.2	c.2048-110C>T		intron_variant	Intron 6 of 6	3		ENSP00000461146.2

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00145 AC: 181 AN: 124866 Hom.: 0 AF XY: 0.00159 AC XY: 106 AN XY: 66590

Gnomad AFR exome AF: 0.000781

Gnomad AMR exome AF: 0.00250

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000118

Gnomad FIN exome AF: 0.000675

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00274

GnomAD4 exome AF: 0.00175 AC: 2051 AN: 1169902 Hom.: 3 Cov.: 23 AF XY: 0.00179 AC XY: 1008 AN XY: 561794

Gnomad4 AFR exome AF: 0.000242

Gnomad4 AMR exome AF: 0.00332

Gnomad4 ASJ exome AF: 0.0000638

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000195

Gnomad4 FIN exome AF: 0.000423

Gnomad4 NFE exome AF: 0.00196

Gnomad4 OTH exome AF: 0.00165

GnomAD4 genome AF: 0.00139 AC: 212 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.00129 AC XY: 96 AN XY: 74470

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000567

Gnomad4 NFE AF: 0.00175

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00151 Hom.: 0

Bravo AF: 0.00168

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000683 AC: 3

ESP6500EA AF: 0.00198 AC: 17

ExAC AF: 0.00142 AC: 159

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 08, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.18
DANN	Benign	0.48
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.0029	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.051
Sift	Benign	0.41	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.076
MVP		0.014
MPC		0.060
ClinPred		0.0022	T
GERP RS		-0.53
Varity_R		0.040
gMVP		0.036

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

Publications

LitVar

Other links and lift over

dbSNP: rs144459500; hg19: chr16-3348996;