NM_031272.5:c.3824C>T

Variant names:

• chr17-58569254-G-A
• rs145643630
• NM_031272.5:c.3824C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_031272.5(TEX14):​c.3824C>T​(p.Ala1275Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000948 in 1,613,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000075 (0 hom.)
• Consequence: TEX14 NM_031272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73
• Publications: 2 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.014891088).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000282 (43/152268) while in subpopulation AMR AF = 0.00196 (30/15288). AF 95% confidence interval is 0.00141. There are 0 homozygotes in GnomAd4. There are 28 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd4 at 43 AD gene.

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.3824C>T	p.Ala1275Val	missense	Exon 26 of 32	NP_112562.3
	TEX14	NM_001201457.2		c.3962C>T	p.Ala1321Val	missense	Exon 27 of 33	NP_001188386.1	Q8IWB6-1
	TEX14	NM_198393.4		c.3944C>T	p.Ala1315Val	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.3824C>T	p.Ala1275Val	missense	Exon 26 of 32	ENSP00000268910.8	Q8IWB6-3
	TEX14	ENST00000240361.12	TSL:1	c.3962C>T	p.Ala1321Val	missense	Exon 27 of 33	ENSP00000240361.8	Q8IWB6-1
	TEX14	ENST00000389934.7	TSL:1	c.3944C>T	p.Ala1315Val	missense	Exon 27 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000207 AC: 52 AN: 250764 AF XY: 0.000184

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000493

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.0000753 AC: 110 AN: 1461496 Hom.: 0 Cov.: 30 AF XY: 0.0000646 AC XY: 47 AN XY: 727046

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000358 AC: 16 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 68 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

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

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111716

Other (OTH) AF: 0.000282 AC: 17 AN: 60390

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152268 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28 AN XY: 74452

African (AFR) AF: 0.00 AC: 0 AN: 41554

American (AMR) AF: 0.00196 AC: 30 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.000399 Hom.: 0

Bravo AF: 0.000310

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000132 AC: 16

EpiCase AF: 0.000109

EpiControl AF: 0.0000594

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	0.14
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	0.033
Eigen_PC	Benign	0.090
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.23
Sift	Benign	0.030	D
Sift4G	Benign	0.13	T
Polyphen		0.81	P
Vest4		0.30
MVP		0.87
MPC		0.14
ClinPred		0.081	T
GERP RS		3.6
Varity_R		0.070
gMVP		0.069
Mutation Taster		=89/11	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: rs145643630; hg19: chr17-56646615;