NM_152325.3:c.499T>C

Variant names:

• chr13-30966251-T-C
• rs982877457
• NM_152325.3:c.499T>C

Variant summary

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

The NM_152325.3(TEX26):​c.499T>C​(p.Ser167Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,838 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. 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. S167T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TEX26 NM_152325.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 0 publications found

Genes affected

TEX26 (HGNC:28622): (testis expressed 26) Predicted to be active in cytoplasm. [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=0.04654473).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152325.3. 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
	TEX26	NM_152325.3	MANE Select	c.499T>C	p.Ser167Pro	missense	Exon 5 of 7	NP_689538.1	Q8N6G2
	TEX26	NM_001353388.2		c.106T>C	p.Ser36Pro	missense	Exon 4 of 6	NP_001340317.1
	TEX26	NM_001353389.2		c.106T>C	p.Ser36Pro	missense	Exon 4 of 6	NP_001340318.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX26	ENST00000380473.8	TSL:1 MANE Select	c.499T>C	p.Ser167Pro	missense	Exon 5 of 7	ENSP00000369840.3	Q8N6G2
	TEX26	ENST00000944411.1		c.91T>C	p.Ser31Pro	missense	Exon 2 of 4	ENSP00000614470.1
	TEX26	ENST00000944412.1		c.91T>C	p.Ser31Pro	missense	Exon 2 of 3	ENSP00000614471.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251396 AF XY: 0.00000736

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: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461838 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.7
DANN	Benign	0.18
DEOGEN2	Benign	0.00044	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.069
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.014
Sift	Benign	0.32	T
Sift4G	Benign	0.26	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.21		Loss of phosphorylation at S167 (P = 0.0238)
MVP		0.088
MPC		0.0057
ClinPred		0.037	T
GERP RS		-4.2
Varity_R		0.061
gMVP		0.16
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs982877457; hg19: chr13-31540388;