chr14-105411396-C-A

Variant names:

• chr14-105411396-C-A
• rs1219472782
• NM_001195082.2:c.179C>A

Variant summary

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

The NM_001195082.2(TEX22):​c.179C>A​(p.Pro60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000856 in 1,168,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. P60L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: TEX22 NM_001195082.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 0 publications found

Genes affected

TEX22 (HGNC:40026): (testis expressed 22) Predicted to be located in cytoplasm. [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=0.21028116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195082.2. 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
	TEX22	NM_001195082.2	MANE Select	c.179C>A	p.Pro60Gln	missense	Exon 3 of 4	NP_001182011.1	C9J3V5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX22	ENST00000451127.3	TSL:2 MANE Select	c.179C>A	p.Pro60Gln	missense	Exon 3 of 4	ENSP00000397002.2	C9J3V5
	TEX22	ENST00000906980.1		c.179C>A	p.Pro60Gln	missense	Exon 3 of 4	ENSP00000577039.1
	TEX22	ENST00000935983.1		c.179C>A	p.Pro60Gln	missense	Exon 2 of 3	ENSP00000606042.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.56e-7 AC: 1 AN: 1168444 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 569016

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23412

American (AMR) AF: 0.00 AC: 0 AN: 13596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16882

East Asian (EAS) AF: 0.00 AC: 0 AN: 26016

South Asian (SAS) AF: 0.0000221 AC: 1 AN: 45204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25958

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 967748

Other (OTH) AF: 0.00 AC: 0 AN: 46482

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.35	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.33
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.047
Sift	Benign	0.037	D
Sift4G	Uncertain	0.036	D
Polyphen		0.96	D
Vest4		0.26
MutPred		0.21		Loss of glycosylation at P60 (P = 0.012)
MVP		0.030
ClinPred		0.60	D
GERP RS		-0.50
Varity_R		0.085
gMVP		0.012
Mutation Taster		=100/0	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: rs1219472782; hg19: chr14-105877733;