chr8-143598012-C-T

Variant names:

• chr8-143598012-C-T
• rs941328379
• NM_032862.5:c.109C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032862.5(TIGD5):​c.109C>T​(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,284,388 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 0.000061 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: TIGD5 NM_032862.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.487
• 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09414485).

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.109C>T	p.Pro37Ser	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.109C>T	p.Pro37Ser	missense	Exon 1 of 1	ENSP00000421489.2	Q53EQ6-1
	EEF1D	ENST00000972259.1		c.-180+921G>A		intron	N/A	ENSP00000642318.1
	EEF1D	ENST00000972260.1		c.-1+921G>A		intron	N/A	ENSP00000642319.1

Frequencies

GnomAD3 genomes AF: 0.0000607 AC: 9 AN: 148272 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.000875

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000300

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000238 AC: 27 AN: 1136116 Hom.: 0 Cov.: 30 AF XY: 0.0000311 AC XY: 17 AN XY: 547100

African (AFR) AF: 0.00 AC: 0 AN: 22806

American (AMR) AF: 0.00 AC: 0 AN: 8408

Ashkenazi Jewish (ASJ) AF: 0.000132 AC: 2 AN: 15150

East Asian (EAS) AF: 0.00 AC: 0 AN: 26392

South Asian (SAS) AF: 0.000342 AC: 14 AN: 40912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24874

Middle Eastern (MID) AF: 0.000987 AC: 3 AN: 3040

European-Non Finnish (NFE) AF: 0.00000316 AC: 3 AN: 949084

Other (OTH) AF: 0.000110 AC: 5 AN: 45450

GnomAD4 genome AF: 0.0000607 AC: 9 AN: 148272 Hom.: 0 Cov.: 32 AF XY: 0.0000968 AC XY: 7 AN XY: 72332

African (AFR) AF: 0.00 AC: 0 AN: 40818

American (AMR) AF: 0.000134 AC: 2 AN: 14946

Ashkenazi Jewish (ASJ) AF: 0.000875 AC: 3 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 5056

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000300 AC: 2 AN: 66688

Other (OTH) AF: 0.00 AC: 0 AN: 2028

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

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	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.3
DANN	Benign	0.96
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.49
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.12	N
REVEL	Benign	0.016
Sift	Benign	0.075	T
Sift4G	Pathogenic	0.0	D
Vest4		0.20
MutPred		0.31		Gain of phosphorylation at P37 (P = 9e-04)
MVP		0.18
MPC		0.83
ClinPred		0.058	T
GERP RS		-0.093
PromoterAI		0.0080	Neutral
Varity_R		0.036
gMVP		0.36
Mutation Taster		=94/6	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: rs941328379; hg19: chr8-144680182;