17-58559546-C-T

Variant names:

• chr17-58559546-C-T
• rs775596455
• NM_031272.5:c.4174G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031272.5(TEX14):​c.4174G>A​(p.Asp1392Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000932 in 1,394,160 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.102
• Publications: 0 publications found

Genes affected

TEX14 (HGNC:11737): (testis expressed 14, intercellular bridge forming factor) The protein encoded by this gene is necessary for intercellular bridges in germ cells, which are required for spermatogenesis. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jan 2011]

SEPTIN4-AS1 (HGNC:51345): (SEPTIN4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14647362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031272.5. 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
	TEX14	NM_031272.5	MANE Select	c.4174G>A	p.Asp1392Asn	missense	Exon 30 of 32	NP_112562.3
	TEX14	NM_001201457.2		c.4312G>A	p.Asp1438Asn	missense	Exon 31 of 33	NP_001188386.1	Q8IWB6-1
	TEX14	NM_198393.4		c.4294G>A	p.Asp1432Asn	missense	Exon 31 of 33	NP_938207.2	Q8IWB6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX14	ENST00000349033.10	TSL:5 MANE Select	c.4174G>A	p.Asp1392Asn	missense	Exon 30 of 32	ENSP00000268910.8	Q8IWB6-3
	TEX14	ENST00000240361.12	TSL:1	c.4312G>A	p.Asp1438Asn	missense	Exon 31 of 33	ENSP00000240361.8	Q8IWB6-1
	TEX14	ENST00000389934.7	TSL:1	c.4294G>A	p.Asp1432Asn	missense	Exon 31 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250622 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000932 AC: 13 AN: 1394160 Hom.: 0 Cov.: 24 AF XY: 0.00000717 AC XY: 5 AN XY: 697338

⚠️ 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: 31522

American (AMR) AF: 0.0000449 AC: 2 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 39156

South Asian (SAS) AF: 0.00 AC: 0 AN: 84160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53354

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00000855 AC: 9 AN: 1052300

Other (OTH) AF: 0.0000345 AC: 2 AN: 57894

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000296585), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.023
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.10
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.035
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.15		Loss of ubiquitination at K1437 (P = 0.0261)
MVP		0.43
MPC		0.058
ClinPred		0.37	T
GERP RS		0.82
Varity_R		0.090
gMVP		0.026
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs775596455; hg19: chr17-56636907;