1-178514734-G-T

Variant names:

• chr1-178514734-G-T
• rs34025088
• NM_032126.5:c.125G>T

Variant summary

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

The NM_032126.5(TEX35):​c.125G>T​(p.Arg42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R42Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TEX35 NM_032126.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 0 publications found

Genes affected

TEX35 (HGNC:25366): (testis expressed 35) Located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

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=0.033326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5	c.125G>T	p.Arg42Leu	missense_variant	Exon 3 of 9	ENST00000319416.7	NP_115502.2
TEX35	NM_001170722.2	c.149G>T	p.Arg50Leu	missense_variant	Exon 3 of 9		NP_001164193.1
TEX35	NM_001170723.2	c.125G>T	p.Arg42Leu	missense_variant	Exon 3 of 9		NP_001164194.1
TEX35	NM_001170724.2	c.125G>T	p.Arg42Leu	missense_variant	Exon 3 of 9		NP_001164195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7	c.125G>T	p.Arg42Leu	missense_variant	Exon 3 of 9	1	NM_032126.5	ENSP00000323795.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.19
DANN	Benign	0.96
DEOGEN2	Benign	0.0040	T;.;.;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.67	T;T;T;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.033	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N;N;.;N;.
PhyloP100		-0.045
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.46	N;N;N;N;N
REVEL	Benign	0.010
Sift	Benign	0.83	T;T;T;T;T
Sift4G	Benign	0.65	T;T;T;T;T
Polyphen		0.0	B;.;.;B;B
Vest4		0.15
MutPred		0.32		Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);.;Loss of MoRF binding (P = 6e-04);.;
MVP		0.061
MPC		0.13
ClinPred		0.067	T
GERP RS		-1.5
Varity_R		0.034
gMVP		0.015
Mutation Taster		=97/3	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: rs34025088; hg19: chr1-178483869;