rs12946522

Variant names:

• chr17-58690742-T-G
• rs12946522
• NM_031272.5:c.-2+1197A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031272.5(TEX14):​c.-2+1197A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,134 control chromosomes in the GnomAD database, including 2,369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2369 hom., cov: 31)
• Consequence: TEX14 NM_031272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• Publications: 25 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]

IGBP1C (HGNC:43611): (IGBP1 family member C) Predicted to enable protein phosphatase 2A binding activity. Predicted to be involved in regulation of dephosphorylation. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX14	NM_031272.5	c.-2+1197A>C		intron_variant	Intron 1 of 31	ENST00000349033.10	NP_112562.3
IGBP1C	NM_001395966.1	c.-231+1197A>C		intron_variant	Intron 1 of 1	ENST00000583666.3	NP_001382895.1
TEX14	NM_001201457.2	c.-2+1197A>C		intron_variant	Intron 1 of 32		NP_001188386.1
TEX14	NM_198393.4	c.-2+1197A>C		intron_variant	Intron 1 of 32		NP_938207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX14	ENST00000349033.10	c.-2+1197A>C		intron_variant	Intron 1 of 31	5	NM_031272.5	ENSP00000268910.8
IGBP1C	ENST00000583666.3	c.-231+1197A>C		intron_variant	Intron 1 of 1	3	NM_001395966.1	ENSP00000492384.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26074 AN: 152016 Hom.: 2366 Cov.: 31

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0777

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.172 AC: 26093 AN: 152134 Hom.: 2369 Cov.: 31 AF XY: 0.175 AC XY: 12982 AN XY: 74388

African (AFR) AF: 0.134 AC: 5564 AN: 41528

American (AMR) AF: 0.169 AC: 2575 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0777 AC: 269 AN: 3464

East Asian (EAS) AF: 0.177 AC: 917 AN: 5176

South Asian (SAS) AF: 0.128 AC: 619 AN: 4826

European-Finnish (FIN) AF: 0.238 AC: 2519 AN: 10572

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13071 AN: 67986

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.172 Hom.: 3970

Bravo AF: 0.159

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.75
DANN	Benign	0.48
PhyloP100		-0.48
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: rs12946522; hg19: chr17-56768103;