17-64193700-T-C

Variant names:

• chr17-64193700-T-C
• rs938294341
• NM_001288732.2:c.2035A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001288732.2(TEX2):​c.2035A>G​(p.Arg679Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TEX2 NM_001288732.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.465
• Publications: 0 publications found

Genes affected

TEX2 (HGNC:30884): (testis expressed 2) Predicted to enable lipid binding activity. Predicted to be involved in lipid transport. Predicted to be located in endoplasmic reticulum membrane and nuclear membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.056307316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX2	NM_001288732.2	c.2035A>G	p.Arg679Gly	missense_variant	Exon 4 of 12	ENST00000584379.6	NP_001275661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX2	ENST00000584379.6	c.2035A>G	p.Arg679Gly	missense_variant	Exon 4 of 12	1	NM_001288732.2	ENSP00000463001.1
TEX2	ENST00000258991.7	c.2035A>G	p.Arg679Gly	missense_variant	Exon 4 of 12	1		ENSP00000258991.3
TEX2	ENST00000583097.5	c.2035A>G	p.Arg679Gly	missense_variant	Exon 4 of 12	1		ENSP00000462665.1
TEX2	ENST00000583501.1	c.535A>G	p.Arg179Gly	missense_variant	Exon 3 of 11	5		ENSP00000462230.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459330 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726010

African (AFR) AF: 0.0000300 AC: 1 AN: 33308

American (AMR) AF: 0.0000452 AC: 2 AN: 44206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110942

Other (OTH) AF: 0.0000497 AC: 3 AN: 60310

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74378

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.000850 AC: 13 AN: 15288

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: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000106

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2035A>G (p.R679G) alteration is located in exon 4 (coding exon 3) of the TEX2 gene. This alteration results from a A to G substitution at nucleotide position 2035, causing the arginine (R) at amino acid position 679 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.019	.;T;T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.82	T;.;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;L;.;L
PhyloP100		0.47
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.30	N;.;.;.
REVEL	Benign	0.062
Sift	Benign	0.30	T;.;.;.
Sift4G	Benign	0.39	T;T;T;T
Polyphen		0.0030	B;B;.;B
Vest4		0.23
MutPred		0.18		Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);Loss of MoRF binding (P = 0.0167);
MVP		0.18
MPC		0.43
ClinPred		0.16	T
GERP RS		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.30
Mutation Taster		=86/14	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: rs938294341; hg19: chr17-62271060;