1-178514070-C-A

Variant names:

• chr1-178514070-C-A
• rs199926250
• NM_032126.5:c.83C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032126.5(TEX35):​c.83C>A​(p.Pro28Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. P28L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TEX35 NM_032126.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.636
• Publications: 5 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18506089).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX35	NM_032126.5	c.83C>A	p.Pro28Gln	missense_variant	Exon 2 of 9	ENST00000319416.7	NP_115502.2
TEX35	NM_001170722.2	c.107C>A	p.Pro36Gln	missense_variant	Exon 2 of 9		NP_001164193.1
TEX35	NM_001170723.2	c.83C>A	p.Pro28Gln	missense_variant	Exon 2 of 9		NP_001164194.1
TEX35	NM_001170724.2	c.83C>A	p.Pro28Gln	missense_variant	Exon 2 of 9		NP_001164195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX35	ENST00000319416.7	c.83C>A	p.Pro28Gln	missense_variant	Exon 2 of 9	1	NM_032126.5	ENSP00000323795.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.;.;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.70	T;T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.;L;.
PhyloP100		0.64
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.8	D;D;D;D;D
REVEL	Benign	0.069
Sift	Benign	0.083	T;T;D;T;T
Sift4G	Benign	0.14	T;T;D;T;T
Polyphen		0.99	D;.;.;D;D
Vest4		0.41
MutPred		0.23		Loss of ubiquitination at K30 (P = 0.0537);Loss of ubiquitination at K30 (P = 0.0537);Loss of ubiquitination at K30 (P = 0.0537);Loss of ubiquitination at K30 (P = 0.0537);.;
MVP		0.21
MPC		0.20
ClinPred		0.52	D
GERP RS		0.24
Varity_R		0.072
gMVP		0.019
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: rs199926250; hg19: chr1-178483205;