chr17-58559547-T-C

Variant names:

• chr17-58559547-T-C
• rs9903050
• NM_031272.5:c.4173A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_031272.5(TEX14):​c.4173A>G​(p.Lys1391Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,514,400 control chromosomes in the GnomAD database, including 28,430 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4231 hom., cov: 32)
  • Exomes 𝑓: 0.18 (24199 hom.)
• Consequence: TEX14 NM_031272.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.581
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-58559547-T-C is Benign according to our data. Variant chr17-58559547-T-C is described in ClinVar as Benign. ClinVar VariationId is 3059694.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.581 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

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.4173A>G	p.Lys1391Lys	synonymous	Exon 30 of 32	NP_112562.3
	TEX14	NM_001201457.2		c.4311A>G	p.Lys1437Lys	synonymous	Exon 31 of 33	NP_001188386.1	Q8IWB6-1
	TEX14	NM_198393.4		c.4293A>G	p.Lys1431Lys	synonymous	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.4173A>G	p.Lys1391Lys	synonymous	Exon 30 of 32	ENSP00000268910.8	Q8IWB6-3
	TEX14	ENST00000240361.12	TSL:1	c.4311A>G	p.Lys1437Lys	synonymous	Exon 31 of 33	ENSP00000240361.8	Q8IWB6-1
	TEX14	ENST00000389934.7	TSL:1	c.4293A>G	p.Lys1431Lys	synonymous	Exon 31 of 33	ENSP00000374584.3	Q8IWB6-2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34313 AN: 151922 Hom.: 4224 Cov.: 32

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.213 AC: 53358 AN: 250412 AF XY: 0.219

Gnomad AFR exome AF: 0.304

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.265

Gnomad EAS exome AF: 0.316

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.181 AC: 246613 AN: 1362360 Hom.: 24199 Cov.: 24 AF XY: 0.187 AC XY: 127813 AN XY: 682740

African (AFR) AF: 0.293 AC: 9043 AN: 30830

American (AMR) AF: 0.120 AC: 5349 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6583 AN: 25384

East Asian (EAS) AF: 0.271 AC: 10564 AN: 38978

South Asian (SAS) AF: 0.305 AC: 25373 AN: 83256

European-Finnish (FIN) AF: 0.190 AC: 10106 AN: 53310

Middle Eastern (MID) AF: 0.271 AC: 1501 AN: 5534

European-Non Finnish (NFE) AF: 0.163 AC: 166383 AN: 1023862

Other (OTH) AF: 0.207 AC: 11711 AN: 56704

GnomAD4 genome AF: 0.226 AC: 34346 AN: 152040 Hom.: 4231 Cov.: 32 AF XY: 0.227 AC XY: 16855 AN XY: 74298

African (AFR) AF: 0.304 AC: 12604 AN: 41428

American (AMR) AF: 0.153 AC: 2334 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3472

East Asian (EAS) AF: 0.312 AC: 1612 AN: 5166

South Asian (SAS) AF: 0.330 AC: 1592 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2051 AN: 10570

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12581 AN: 67984

Other (OTH) AF: 0.224 AC: 473 AN: 2116

Alfa AF: 0.199 Hom.: 4989

Bravo AF: 0.224

Asia WGS AF: 0.326 AC: 1132 AN: 3476

EpiCase AF: 0.190

EpiControl AF: 0.191

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TEX14-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs9903050; hg19: chr17-56636908; COSMIC: COSV53613714; COSMIC: COSV53613714;