NM_031272.5:c.4301G>T

Variant names:

• chr17-58557817-C-A
• rs778068338
• NM_031272.5:c.4301G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_031272.5(TEX14):​c.4301G>T​(p.Gly1434Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,982 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• Publications: 1 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 -1 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.4301G>T	p.Gly1434Val	missense	Exon 31 of 32	NP_112562.3
	TEX14	NM_001201457.2		c.4439G>T	p.Gly1480Val	missense	Exon 32 of 33	NP_001188386.1	Q8IWB6-1
	TEX14	NM_198393.4		c.4421G>T	p.Gly1474Val	missense	Exon 32 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.4301G>T	p.Gly1434Val	missense	Exon 31 of 32	ENSP00000268910.8	Q8IWB6-3
	TEX14	ENST00000240361.12	TSL:1	c.4439G>T	p.Gly1480Val	missense	Exon 32 of 33	ENSP00000240361.8	Q8IWB6-1
	TEX14	ENST00000389934.7	TSL:1	c.4421G>T	p.Gly1474Val	missense	Exon 32 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250582 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

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: 0.00000411 AC: 6 AN: 1459982 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726232

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.0000897 AC: 4 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 85978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110916

Other (OTH) AF: 0.00 AC: 0 AN: 60320

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

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	0.31
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.3
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.40		Loss of helix (P = 0.0017)
MVP		0.57
MPC		0.34
ClinPred		0.86	D
GERP RS		4.7
Varity_R		0.55
gMVP		0.13
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs778068338; hg19: chr17-56635178;