chr17-58569236-A-G

Variant names:

• chr17-58569236-A-G
• rs780493238
• NM_031272.5:c.3842T>C

Variant summary

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

The NM_031272.5(TEX14):​c.3842T>C​(p.Ile1281Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,754 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.689
• 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: 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=0.111395955).

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.3842T>C	p.Ile1281Thr	missense	Exon 26 of 32	NP_112562.3
	TEX14	NM_001201457.2		c.3980T>C	p.Ile1327Thr	missense	Exon 27 of 33	NP_001188386.1	Q8IWB6-1
	TEX14	NM_198393.4		c.3962T>C	p.Ile1321Thr	missense	Exon 27 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.3842T>C	p.Ile1281Thr	missense	Exon 26 of 32	ENSP00000268910.8	Q8IWB6-3
	TEX14	ENST00000240361.12	TSL:1	c.3980T>C	p.Ile1327Thr	missense	Exon 27 of 33	ENSP00000240361.8	Q8IWB6-1
	TEX14	ENST00000389934.7	TSL:1	c.3962T>C	p.Ile1321Thr	missense	Exon 27 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251208 AF XY: 0.00

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: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461754 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727182

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

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: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111904

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

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	0.071
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.094	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.047
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.69
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.025
Sift	Uncertain	0.012	D
Sift4G	Benign	0.13	T
Polyphen		0.25	B
Vest4		0.30
MutPred		0.25		Gain of loop (P = 0.0045)
MVP		0.46
MPC		0.062
ClinPred		0.16	T
GERP RS		3.3
Varity_R		0.083
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs780493238; hg19: chr17-56646597;