8-143598570-C-T

Variant names:

• chr8-143598570-C-T
• rs762443927
• NM_032862.5:c.667C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032862.5(TIGD5):​c.667C>T​(p.Pro223Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,328,808 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 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: TIGD5 NM_032862.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.599
• Publications: 0 publications found

Genes affected

TIGD5 (HGNC:18336): (tigger transposable element derived 5) 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]

EEF1D (HGNC:3211): (eukaryotic translation elongation factor 1 delta) This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit, delta, functions as guanine nucleotide exchange factor. It is reported that following HIV-1 infection, this subunit interacts with HIV-1 Tat. This interaction results in repression of translation of host cell proteins and enhanced translation of viral proteins. Several alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. Related pseudogenes have been defined on chromosomes 1, 6, 7, 9, 11, 13, 17, 19.[provided by RefSeq, Aug 2010]

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=0.0055030584).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032862.5. 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
	TIGD5	NM_032862.5	MANE Select	c.667C>T	p.Pro223Ser	missense	Exon 1 of 1	NP_116251.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIGD5	ENST00000504548.4	TSL:6 MANE Select	c.667C>T	p.Pro223Ser	missense	Exon 1 of 1	ENSP00000421489.2	Q53EQ6-1
	EEF1D	ENST00000972259.1		c.-180+363G>A		intron	N/A	ENSP00000642318.1
	EEF1D	ENST00000972260.1		c.-1+363G>A		intron	N/A	ENSP00000642319.1

Frequencies

GnomAD3 genomes AF: 0.0000397 AC: 6 AN: 151256 Hom.: 0 Cov.: 33

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000738

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000952 AC: 1 AN: 10500 AF XY: 0.000142

Gnomad AFR exome AF: 0.00

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: 0.00439

GnomAD4 exome AF: 0.0000195 AC: 23 AN: 1177552 Hom.: 0 Cov.: 32 AF XY: 0.0000263 AC XY: 15 AN XY: 570004

African (AFR) AF: 0.00 AC: 0 AN: 22896

American (AMR) AF: 0.00 AC: 0 AN: 9004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16334

East Asian (EAS) AF: 0.00 AC: 0 AN: 26304

South Asian (SAS) AF: 0.00 AC: 0 AN: 45258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3276

European-Non Finnish (NFE) AF: 0.0000225 AC: 22 AN: 979568

Other (OTH) AF: 0.0000210 AC: 1 AN: 47710

GnomAD4 genome AF: 0.0000397 AC: 6 AN: 151256 Hom.: 0 Cov.: 33 AF XY: 0.0000271 AC XY: 2 AN XY: 73870

African (AFR) AF: 0.00 AC: 0 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15194

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10254

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67712

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.0000868 AC: 1

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	0.068
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.4
DANN	Benign	0.95
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.0055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.60
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.034
Sift	Benign	0.77	T
Sift4G	Benign	0.24	T
Vest4		0.14
MVP		0.088
MPC		0.83
ClinPred		0.031	T
GERP RS		-4.9
Varity_R		0.021
gMVP		0.057
Mutation Taster		=99/1	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: rs762443927; hg19: chr8-144680740;